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.

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 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.

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.