Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation

OBJECTIVE To observe the clinical efficacy of Yangyin Yifei Decoction in treating type 2 diabetes mellitus(T2DM)patients with of qi-yin deficiency and elevated serum keratin 19 fragment(Cyfra21-1).METHODS Sixty patients with T2DM of qi-yin deficiency type and elevated serum Cyfra21-1 who met the inclusion criteria were selected and randomly divided into an observation group and a control group,30 cases in each group.The control group was given oral hypoglycemic treatment with metformin hydrochlo-ride sustained-release tablets and dapagliflozin tablets,and the observation group was given Yangyin Yifei Decoction on the basis of the treatment of the control group.The treatment course of both groups was 12 weeks.Before and after treatment,the changes of traditional Chinese medicine(TCM)syndrome scores,fasting blood glucose(FBG)and 2-hour postprandial glucose(2 h PG),glycosylated he-moglobin(HbAlc),serum Cyfra21-1 and Cyfra21-1 specific T cell response,triglycerides(TG),total cholesterol(TC),alanine ami-notransferase(ALT),aspartate aminotransferase(AST),urea(UR),and creatinine(CREA)were observed in the two groups.RE-SULTS After treatment,FBG,2 h PG,HbAlc,and TCM syndrome scores of the two groups of patients decreased significantly(P<0.05,P<0.01),and the observation group was better than the control group(P<0.05,P<0.01);TG and TC in the observation group were significantly reduced(P<0.01),serum Cyfra21-1 was significantly decreased(P<0.01),and Cyfra21-1-specific T cells in PBMCs were significantly increased(P<0.01),which was better than the control group(P<0.01);there was no significant change in liver and kidney function in the two groups.CONCLUSION Yangyin Yifei Decoction combined with basic hypoglycemic regimen can significantly improve blood glucose and lipid metabolism in T2DM patients with qi-yin deficiency and elevated serum Cyfra21-1,enhance the function of Cyfra21-1-specific T cells,and improve the body's immunity,with high safety.

Objective To explore the medication rules and mechanism of Xin'an physicians in the treatment of diabetes mellitus.Methods The prescriptions for the treatment of diabetes mellitus in Xin'an medical writings were collected.The core drug prescriptions were obtained by using IBM SPSS Modeler 18.0 for dispensing association rules as well as complex network analysis,and the cluster analysis of high-frequency traditional Chinese medicines was carried out by using IBM SPSS Statistics 25.0.The active ingredients and targets of the core drugs were extracted from the BATMAN-TCM database.The GeneCards database was used to search for diabetes gene targets,and after obtaining the intersecting targets,the STRING online platform was imported to construct the protein interactions network,and screened the core genes by using the Cytoscape 3.9.1 software,and imported into the DAVID database for GO function and KEGG pathway enrichment analysis.Results A total of 135 valid prescriptions were included,involving 184 flavors of traditional Chinese medicines,with cold and mild properties.Sweet,bitter and pungent flavors,and the main attributes of lung,spleen,kidney,stomach and heart meridians.The association rules mined 14 pairs of commonly used medicine pairs.Cluster analysis clustered the top 20 traditional Chinese medicines into five cluster groups.Complex network visualization analysis formed a core prescription consisting of honey-fried licorice root,ginseng,rhizoma anemarrhenae,ophiopogon japonicus,poria cocos.The core prescription drugs were screened for 164 effective active ingredients,1,498 action targets,1,995 diabetes gene targets,404 intersecting targets,10 core targets were extracted,and a total of 1,363 items covering BP were obtained from GO functional enrichment analysis,129 items involving CC,264 items containing MF,and 206 items of KEGG signaling pathway.Conclusion The prescriptions and medicines used by Xin'an doctors in the treatment of diabetes mellitus reflect the academic idea of"treating both the symptoms and the root cause"as well as the therapeutic thought of"using cold and warmth,supplementing with sweetness and warmth,opening up and lowering with bitterness,cultivating the earth and generating gold,and consolidating the root and cultivating the elements",which provide references for the treatment of diabetes mellitus in today's clinics.

Objective To establish the UPLC fingerprint of 10 batches of Gongliuning capsule and the content determination methods of 10 main components;To conduct network pharmacological research;To provide scientific basis for predicting the quality marker of Gongliuning capsule.Methods UPLC-DAD technique was used to establish the fingerprint of different batches of Gongliuning capsule samples and obtain the complete chemical composition information of Gongliuning capsule.With the help of network pharmacological research techniques,the target of chemical components of Gongliuning capsule and related pathways screened from various databases were predicted and analyzed,and the protein interaction network and composition-target-pathway diagram were constructed to predict the effective components of Gongliuning capsule.Based on the obtained pharmacodynamic substances,the content determination method of Gongliuning capsule was established to evaluate the quality of Gongliuning capsule.Results The fingerprints of Gongliuning capsule identified 17 common peaks.Combined with network pharmacology method,the candidate chemical components were analyzed,10 core targets and 42 metabolic pathways were obtained.Based on the testability of components and the availability of reference substances,10 compounds with high contribution were selected for content determination.Methodological verification results showed that all the 10 compounds had good linear relationship(r2>0.999 4)in the detection range,with good precision,accuracy and stability.Conclusion The established UPLC fingerprint,network pharmacology and multiple component content determination methods are highly specific,accurate and reliable.Combined with chemical pattern recognition,they can be effectively used for quality control and quality marker prediction of Gongliuning capsules.

The gastrin-releasing peptide receptor(GRPR)is highly expressed in various malignant tumors(e.g.,glioblastoma,prostate cancer,and breast cancer)and has emerged as an important molecular target for precision cancer diagnosis and therapy.In recent years,the combined application of radionuclide-la-beled GRPR ligands with positron emission tomography/computed tomography(PET/CT)has achieved ground-breaking progress in noninvasive diagnosis,accurate staging,and therapeutic monitoring of GRPR-positive tumors.Meanwhile,GRPR-targeted radionuclide therapeutics have demonstrated significant therapeutic potential and promising clinical applications in trials.This GRPR-based theranostic strategy pioneers a novel ap-proach for precision medicine in GRPR-overexpressing tumors.

In Western developed countries,precision nuclear medicine diagnosis and treatment for neuroendocrine neoplasms(NENs)have been widely adopted in clinical practice.Over the past two decades,China has made significant progress in both research and clinical application of nuclear medicine-based NENs management.With internationally approved diagnostic and therapeutic agents soon entering the Chinese market and the ongoing clinical trials of domestically developed innovative drugs,there is an urgent need to establish standardized diagnostic and treatment guideline.To address this,the Chinese Society of Nuclear Medicine and the Chinese Neuroendocrine Tumor Society have collaborated to develop the Clinical Guideline for Precision Nuclear Medicine Diagnosis and Treatment of Neuroendocrine Neoplasms(2025 Edition).The guideline integrates the latest research advances and international recommendations with China's clinical practice,aiming to standardize and optimize NENs management through nuclear medicine in China.

Diabetes mellitus （DM） is a metabolic disease caused by absolute or relative insulin deficiency and reduced insulin sensitivity in peripheral cells， posing a serious threat to global health. Chronic complications arising in the later stages of DM can lead to the decline or even loss of function in multiple organs， including the eyes， heart， liver， kidneys， nerves， and feet， making them the primary cause of mortality in DM patients. Although modern medicine has made some progress in the treatment of these complications， challenges such as high costs and adverse drug reactions remain. Thus， identifying highly effective drugs with minimal adverse effects has become a top priority. Astragalus membranaceus is a shining gem in the treasure trove of Chinese medicine. Numerous studies have shown that its primary active component， astragaloside Ⅳ， possesses various biological activities， including anti-inflammatory， antioxidant， and antiviral effects， as well as benefits for cardiac and cerebral function， nerve conduction， and myocardial protection. Meanwhile， the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a crucial role in regulating oxidative stress， inflammatory responses， apoptosis， and autophagy. Extensive research has highlighted the significant role of this pathway in various DM complications， leading to widespread studies on its interaction with astragaloside Ⅳ. This review summarizes research findings on how astragaloside Ⅳ alleviates pancreatic cytotoxicity in DM patients by modulating the PI3K/Akt pathway. Additionally， it highlights its protective effects on basic cardiac function， inhibition of retinal cell damage， improvement of cerebral nerve dysfunction， reduction of chronic kidney and liver damage， and mitigation of neurovascular toxicity in the lower limbs. These insights provide a valuable reference for the clinical application of A. membranaceus and its active monomer， astragaloside Ⅳ， in the treatment of DM and its complications.