OBJECTIVE To investigate the ameliorative effect and mechanism of short-acting exenatide on diabetic cognitive dysfunction. METHODS Spontaneously diabetic db / db mice were randomly divided into model group （normal saline） and exenatide group （50 μg/kg）， with db / m mice as the normal control group （normal saline）， with 8 mice in each group. Mice in each group were subcutaneously injected with corresponding drugs or normal saline twice daily for 8 consecutive weeks. Body weight and fasting blood glucose were measured at a fixed time every week. Cognitive function was evaluated by Morris water maze test. The levels of oxidative st ress indicators [malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH） ] ， cyclic adenosine monophosphate （cAMP） and protein kinase A （PKA） were detected in hippocampus tissue of mice. The hippocampal neuronal HT22 cells of mice were divided into control group （25 mmol/L glucose）， high glucose group （125 mmol/L glucose）， high glucose+exenatide group （125 mmol/L glucose+20 nmol/L exenatide）， high glucose+exenatide+H89 （PKA inhibitor） group （125 mmol/L glucose+20 nmol/L exenatide+10 μmol/L H89）， and high glucose+H89 group （125 mmol/L glucose+10 μmol/L H89）. After 48 h of intervention with corresponding solutions/culture medium， the levels of oxidative stress indicators， cAMP and PKA， the activities of mitochondrial respiratory enzymes Ⅱ and Ⅳ， and the phosphorylation level of dynamin-related protein 1 （Drp1） were measured. RESULTS Animal experiments showed that compared with the normal control group， the model group exhibited significantly increased body weight， fasting blood glucose and MDA level in the hippocampus （ P ＜0.05）， as well as significantly prolonged escape latency （ P ＜0.05）； swimming speed significantly slowed down， the time spent in the target quadrant， the number of platform crossings， and the levels of SOD， GSH， cAMP and PKA in the hippocampus were significantly decreased （ P ＜0.05）. Compared with model group， all the above indicators （except for swimming speed） in the exenatide group were significantly reversed （ P ＜0.05）. Cell experiments showed that compared with high glucose group， the high glucose+exenatide group had significantly decreased MDA level （ P ＜0.05）， and significantly increased levels of SOD， GSH， cAMP and PKA， the activities of mitochondrial respiratory enzymes Ⅱ and Ⅳ， and phosphorylation level of Drp1 （ P ＜0.05）. Compared with high glucose+exenatide group， the above indicators in the high glucose+exenatide+H89 group were significantly reversed （ P ＜0.05）. CONCLUSIONS Short-acting exenatide can activate the cAMP/PKA pathway， promote Drp1 phosphorylation， and increase the activities of mitochondrial respiratory enzymes， thereby maintaining mitochondrial stability， reducing oxidative stress injury， and ultimately improving diabetic cognitive dysfunction.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Renal metastasis from differentiated thyroid cancer (DTC) is uncommon and is hard to be distinguished from primary renal cell carcinoma. There is no consensus on diagnosis and treatment, and decisions about surgery and 131I therapy doses usually depend on experience. To better understand clinical characteristics and current treatment status, this study systematically reviews existing studies, exploring epidemiological features, clinical symptoms, imaging findings (including lesions characteristics across various imaging modalities), therapeutic strategies, and prognosis of DTC renal metastases, providing evidence-based references for clinical practice.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

OBJECTIVES: To explore the mechanism by which Pulsatilla saponin D (PSD) inhibits invasion and metastasis of triple-negative breast cancer (TNBC). METHODS: The public databases were used to identify the potential targets of PSD and the invasion and metastasis targets of TNBC to obtain the intersection targets between PSD and TNBC. The "PSD-target-disease" interaction network was constructed and protein-protein interaction (PPI) analysis was performed to obtain the core targets, which were analyzed for KEGG pathway and GO functional enrichment. Molecular docking study of the core targets and PSD was performed, and the therapeutic effect and mechanism of PSD were verified using Transwell assay and Western blotting in cultured TNBC cells. RESULTS: Network pharmacology analysis identified a total of 285 potential PSD targets and 26 drug-disease intersection core targets. GO analysis yielded 175 entries related to the binding of biomolecules (protein, DNA and RNA), enzyme activities, and regulation of gene transcription. KEGG analysis yielded 46 entries involving pathways in cancer, chemical carcinogenesis-receptor activation, microRNAs in cancer, chemical carcinogenesis-reactive oxygen species, PD-L1 expression and PD-1 checkpoint pathway in cancer. Molecular docking showed high binding affinities of PSD to MTOR, HDAC2, ABL1, CDK1, TLR4, TERT, PIK3R1, NFE2L2 and PTPN1. In cultured TNBC cells, treatment with PSD significantly inhibited cell invasion and migration and lowered the expressions of MMP2, MMP9, N-cadherin and the core proteins p-mTOR, ABL1, TERT, PTPN1, HDAC2, PIK3R1, CDK1, TLR4 as well as NFE2L2 expressionin the cell nuclei. CONCLUSIONS The inhibitory effects of PSD on TNBC invasion and metastasis are mediated by multiple targets and pathways.
Humans ; Triple Negative Breast Neoplasms/metabolism* ; Saponins/pharmacology* ; Pulsatilla/chemistry* ; Female ; Molecular Docking Simulation ; Cell Line, Tumor ; Neoplasm Invasiveness ; Protein Interaction Maps ; Neoplasm Metastasis ; Signal Transduction/drug effects* ; Cell Movement/drug effects*

Objective To investigate the relationships of computed tomography (CT) angiography (CTA)-derived coronary plaque properties with platelet function and whole blood cell-derived inflammatory markers in elderly patients with coronary heart disease. Methods The clinical data of 142 elderly patients with coronary heart disease who underwent coronary CTA examination in the hospital between April 2022 and April 2025 were retrospectively analyzed. The CT value of CTA, platelet function parameters (mean platelet volume, platelet-derived growth factor BB, von Willebrand factor), and whole blood cell-derived inflammatory markers were recorded at admission. The correlations of the CT value of CTA-derived coronary plaque properties with platelet function parameters and whole blood cell-derived inflammatory markers in elderly patients with coronary heart disease were analyzed using Pearson correlation coefficients. Based on the evaluation of CTA-derived coronary plaque properties, the patients were divided into a soft plaque group (CT value ≤ 60 HU), a calcified plaque group (CT value ≥ 130 HU), and a mixed plaque group (60 HU < CT value < 130 HU). The platelet function parameters (mean platelet volume, platelet-derived growth factor BB, von Willebrand factor) and whole blood cell-derived inflammatory markers (systemic immune-inflammation index, systemic inflammation response index, neutrophil-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio) on admission were compared among the three groups. Results The coronary CTA examination showed 37 (26.06%) cases in the calcified plaque group, 47 (33.10%) cases in the soft plaque group, and 58 (40.84%) cases in the mixed plaque group. The CT values were (189.57 ± 22.14) HU for the calcified plaque group, (31.74 ± 4.12) HU for the soft plaque group, and (94.52 ± 8.29) HU for the mixed plaque group. The levels of platelet function parameters and whole blood cell-derived inflammatory markers at admission were in the following order: soft plaque group > mixed plaque group > calcified plaque group, and the differences were statistically significant (P < 0.05). After adjustment for sex, age, cardiac function grading, hypertension, diabetes, and blood lipids as covariates, partial correlation analysis revealed that the CT value of CTA-derived coronary plaque properties in elderly patients with coronary heart disease was negatively correlated with the levels of platelet function parameters and whole blood cell-derived inflammatory markers (P < 0.05). Conclusion In this study, the coronary plaque CT value in elderly patients with coronary heart disease was negatively correlated with the levels of platelet function parameters and whole blood cell-derived inflammatory markers. Furthermore, increasing plaque instability may be associated with more pronounced platelet activation and a heightened systemic inflammatory state.

Objective To explore the mechanism by which Pulsatilla saponin D(PSD)inhibits invasion and metastasis of triple-negative breast cancer(TNBC).Methods The public databases were used to identify the potential targets of PSD and the invasion and metastasis targets of TNBC to obtain the intersection targets between PSD and TNBC.The"PSD-target-disease"interaction network was constructed and protein-protein interaction(PPI)analysis was performed to obtain the core targets,which were analyzed for KEGG pathway and GO functional enrichment.Molecular docking study of the core targets and PSD was performed,and the therapeutic effect and mechanism of PSD were verified using Transwell assay and Western blotting in cultured TNBC cells.Results Network pharmacology analysis identified a total of 285 potential PSD targets and 26 drug-disease intersection core targets.GO analysis yielded 175 entries related to the binding of biomolecules(protein,DNA and RNA),enzyme activities,and regulation of gene transcription.KEGG analysis yielded 46 entries involving pathways in cancer,chemical carcinogenesis-receptor activation,microRNAs in cancer,chemical carcinogenesis-reactive oxygen species,PD-L1 expression and PD-1 checkpoint pathway in cancer.Molecular docking showed high binding affinities of PSD to MTOR,HDAC2,ABL1,CDK1,TLR4,TERT,PIK3R1,NFE2L2 and PTPN1.In cultured TNBC cells,treatment with PSD significantly inhibited cell invasion and migration and lowered the expressions of MMP2,MMP9,N-cadherin and the core proteins p-mTOR,ABL1,TERT,PTPN1,HDAC2,PIK3R1,CDK1,TLR4 as well as NFE2L2 expressionin the cell nuclei.Conclusion The inhibitory effects of PSD on TNBC invasion and metastasis are mediated by multiple targets and pathways.

Objective To establish a UV method for the determination of the functional compositions(cinnamic acid derivatives,total flavonoids)in Ligustrum robustum,to predict the contents of trans-p-hydroxycinnamic acid,trans-p-hydroxycinnamic acid esters,and rhoifolin based on UV/HPLC,and to optimize the technological conditions of ultrasonic-assistant extraction of L.robustum.Methods ①In the determination of the functional compositions in L.robustum,total cinnamic acid derivatives were determined by dual-wavelength isobestic point UV method(detection wavelength 316 nm,reference wavelength 268 nm),and total flavonoids were determined by single-wavelength UV method(detection wavelength 268 nm),while rhoifolin was determined by HPLC(C 18 column,eluting with methanol-0.1％acetic acid=40∶60,detection wavelength 310 nm).②The conversion factors were used to establish a UV/HPLC-based prediction model,and the precision of the predicted results was evaluated with other 3 test samples.③ The technological conditions of ultrasonic-assisted extraction were optimized by an orthogonal test.Results ① The linear ranges of total cinnamic acid derivatives,total flavonoids,and rhoifolin were 4.64-20.88,8.24-28.84,5.15-51.50 μg·mL-1(r≥0.999 5),respectively.RSDs of the precision,stability,and reproducibility tests were no more than 1.4％.The recoveries were 97.9％-100.5％(RSD≤ 1.2％,n=6).②The relative errors of the values predicted by UV/HPLC from the results measured by HPLC were from-5.3％to 1.7％.There was no significant difference between the UV/HPLC predicted values and the HPLC determined results(P＞0.05)for the contents of trans-p-hydroxycinnamic acid and rhoifolin.③The optimal technological conditions of ultrasonic-assistant extraction of L.robustum were as follows:ethanol concentration 80％,temperature 50 ℃,liquid-solid ratio 20 mL·g 1,extraction frequency 2 times,extraction time 20 min.The total yield of functional compositions under above conditions was 42.0％.Conclusion The above determination methods are accurate and rapid,and the above extraction technology is effective,energy-saving and rapid,which provide an experimental base for the quality control and application of L.robustum.

Objective:To study the effects of Linc00426 on the migration,invasion and proliferation of oral squamous carcinoma cells(OSCC).Methods:TCGA database was used to query the differential expression of Linc00426.RT-qPCR was used to detect the expression level of Linc00426 in normal human oral keratinocytes(NHOK)cells and various OSCC cells lines,the knockout effi-ciency of Linc00426 at 3 sites and the expression level of miR-455-5p.Transwell test and EdU test were used to detect the changes of the migration,invasion and proliferation of CAL27 cells.Bioinformatics databases was used to predict subcellular localization and downstream miRNAs and target proteins of Linc00426.Western blot assay was used to detect the changes of USP3 expression levels in CAL27 cells.Results:The expression level of Linc00426 was increased in OSCC tissue(P＜0.05),and its expression in CAL27,HN4 and HN30 cells was higher than that in NHOK cells(P＜0.05).Knocking out Linc00426 inhibited the migration,invasion,and proliferation ability of CAL27 cells(P＜0.05).The bioinformatics database indicates that the subcellular localization of Linc00426 is in the cytoplasm;Linc00426 is negatively correlated with miR-455-5p,and miR-455-5p is negatively correlated with USP3,in which there are targeted binding sites.Knocking out miR-455-5p promoted the migration,invasion and proliferation of CAL27 cells(P＜0.05).Knocking out USP3 inhibited the migration,invasion and proliferation of CAL27 cells(P＜0.05).Knock out Linc00426 reduced the expression level of USP3,while knocking out miR-455-5p increased the expression level of USP3(P＜0.05).Conclusion:Linc00426 plays a role as an oncogene in OSCC cells and could inhibit the migration,invasion and proliferation of the cells by targeting USP3 to regulate miR-455-5p.