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.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective To evaluate the effect of Intravascular lithotripsy(IVL)in the treatment of calcified nodules,and to observe the presence of coronary dissection after IVL treatment.Methods A total of 106 patients with coronary atherosclerotic heart disease(coronary heart disease)admitted to the cardiovascular Department of Shougang Hospital,Peking University from March 2023 to July 2024 were retrospectively analyzed.A total of 106 patients with moderate to severe stenosis accompanied by calcification as detected by coronary angiography were treated with IVL after intravascular ultrasound(IVUS)examination.Patients were divided into two groups according to whether there were calcified nodules in the coronary lesions:39 cases in the calcified nodules group and 67 cases in the non-calcified nodules group.The occurrence of coronary dissection during surgery was observed between the two groups,and other perioperative related complications and major adverse cardiovascular events(MACE)within 1 month after percutaneous coronary intervention(PCI)were compared between the two groups.Results The levels of renal insufficiency(25.6％vs.9.0％,P=0.021)and creatinine[(119.71±134.75)μmol/L vs.(71.82±16.53)μmol/L,P=0.033]in the calcified nodule group were higher than those in the non-calcified nodule group,the difference was statistically significant,and there was no difference in other baseline data.The target vessels in the calcified nodule group were mainly left anterior descending branch and right coronary artery,while those in the non-calcified nodule group were mainly left anterior descending branch,with few circumflex branches in both groups,and there was statistical significance in the distribution of target vessels in the left anterior descending branch and right coronary artery between the two groups(P=0.020).In terms of eccentric calcification(P=0.048)and asymmetric calcification(48.7％vs.28.4％,P=0.035)between the two groups,the calcified nodule group was higher than the non-calcified nodule group,the difference was statistically significant(P＜0.05).In terms of whether more than 20 pulses were needed and whether there was slippage during IVL,the calcified nodule group was higher than the non-calcified nodule group,the difference was statistically significant(P=0.022).The success rate of interventional therapy was 100％in both groups.After IVL treatment,the calcified nodule group was higher than the non-calcified nodule group in terms of the occurrence of coronary artery dissection,the difference was statistically significant(P＜0.009).The MACE of the two groups within 1 month after PCI was slightly higher in the calcified nodule group than in the non-calcified nodule group,but the difference was not statistically significant(P=0.235).Conclusions IVL is feasible and effective for the treatment of calcified coronary nodules.However,in the course of treatment,the occurrence of coronary dissection should be vigilant,identified as early as possible,and treated in time.

Objective To investigate the expression levels of T cell receptor(TCR)ζchain and Zeta-chain-associated protein kinase 70(ZAP70)in peripheral blood of patients with primary Sj?gren syndrome(PSS).Methods Thirty-six patients with PSS who were treated at Jiujiang NO.1 People's Hospital from January to June 2024 were enrolled in observation group,and 30 healthy subjects during the same period were enrolled in control group.Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression levels of TCRζ chain and ZAP70 in peripheral blood mononuclear cells,and flow cytometry was used to detect peripheral blood T cell subsets.Pearson correlation was used to analyze the correlation between TCRζ chain,ZAP70 and other detection indicators.Results The relative expression levels of TCRζ chain and ZAP70 in observation group were significantly lower than those in control group(P＜0.05),while CD8+and interleukin-6(IL-6)were significantly higher than those in control group(P＜0.05).Pearson correlation analysis showed that TCRζ chain was positively correlated with CD4+,and negatively correlated with CD8+and IL-6(P＜0.05).ZAP70 was negatively correlated with CD8+and IL-6(P＜0.05).Conclusion The expressions of TCRζ chain and ZAP70 are down-regulated in PSS patients,which may exacerbate the immune disorder of PSS through abnormal T cell signal transduction.

Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

The chemical constituents of the petroleum ether extract derived from the 90% ethanol extract of Elephantopus scaber were investigated. By silica gel column chromatography, C_(18), MCI column chromatography and semi-preparative high performance liquid chromatography, ten compounds were isolated. Their structures were identified as 3β-hydroxy-6β,7β-epoxytaraxeran-14-ene(1), 3β-hydroxyolean-12-en-28-oic acid(2), D-friedoolean-14-ene-3β,7α-diol(3), 3β-hydroxy-11α-methoxyolean-12-ene(4), 3β-hydroxyolean-11,13(18)-diene(5), 11α-hydroxy-β-amyrin(6), betulinic acid(7), 3β-hydroxy-30-norlupan-20-one(8), 6-acetonylchelerythrine(9), and 4',5'-dehydrodiodictyonema A(10) by analysis of the 1D NMR, 2D NMR, MS, and IR spectral data. Among them, compound 1 was a new triterpene and other compounds except compounds 2 and 7 were isolated from this plant for the first time.
Triterpenes/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Molecular Structure ; Asteraceae/chemistry* ; Chromatography, High Pressure Liquid ; Magnetic Resonance Spectroscopy

Hemodynamics numerical simulation,a multidisciplinary research approach integrating fluid dynamics,clinical medicine,and computer simulation techniques,offers an objective and quantitative analysis of cardiovascular blood flow dynamics through calculating data such as flow rate,pressure,resistance,and wall stress.This review provides a comprehensive overview of the modeling methods and characteristics of numerical simulations within the cardiovascular system.Additionally,it also summarizes the research advancements and potential clinical applications of numerical simulations in the context of various cardiovascular diseases,including vascular aneurysms,aortic dissection,atherosclerosis,structural heart diseases,heart failure,ventricular assist devices,cardiogenic shock,and extracorporeal membrane oxygenation.The goal is to facilitate the deep integration of clinical medicine with engineering technologies,thereby fostering innovative solutions for the precise diagnosis and treatment of cardiovascular disease.

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: Cancer remains a significant global health challenge, necessitating the development of effective treatment approaches. Developing synergistic therapy can provide a highly promising strategy for anti-cancer treatment through combining the benefits of various mechanisms. METHODS: In this study, we developed a synergistic strategy for chemo-photothermal therapy by constructing nanocomposites using gold nanorods (GNRs) and tetrahedral framework nucleic acids (tFNA) loaded with the anti-tumor drug doxorubicin (DOX). RESULTS: Our in vitro studies have systematically clarified the anti-cancer behaviors of tFNA-DOX@GNR nanocomposites, characterized by their enhanced cellular uptake and proficient lysosomal escape capabilities. It was found that the key role of tFNA-DOX@GNR nanocomposites in tumor ablation is primarily due to their capacity to induce cytotoxicity in tumor cells via a photothermal effect, which generates instantaneous high temperatures. This mechanism introduces various responses in tumor cells, facilitated by the thermal effect and the integrated chemotherapeutic action of DOX. These reactions include the induction of endoplasmic reticulum stress, characterized by elevated reactive oxygen species levels, the promotion of apoptotic cell death, and the suppression of tumor cell proliferation. CONCLUSION This work exhibits the potential of synergistic therapy utilizing nanocomposites for cancer treatment and offers a promising avenue for future therapeutic strategies.
Doxorubicin/chemistry* ; Gold/chemistry* ; Nanotubes/chemistry* ; Humans ; Nanocomposites/chemistry* ; Cell Line, Tumor ; Nucleic Acids/chemistry* ; Antibiotics, Antineoplastic/pharmacology* ; Antineoplastic Agents/administration & dosage*