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Fisetin micelles precisely exhibit a radiosensitization effect by inhibiting PDGFRβ/STAT1/STAT3/Bcl-2 signaling pathway in tumor

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Chinese Chemical Letters 2025年第2期36卷 262-269页

作者： Yuanyuan Zeng Fang Liu Jun Wang Bianfei Shao Tao He Zhongzheng Xiang Yan Wang Shunyao Zhu Tian Yang Siting Yu Changyang Gong Lei Liu Department of Radiation Oncology Cancer CenterState Key Laboratory of BiotherapyWest China HospitalSichuan University Department of Radiation Oncology The Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer Hospital Chongqing Key Laboratory of translational Research for Cancer Metastasis and individualized Treatment Chongqing University Cancer Hospital Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan University Department of Pharmacy The First Affiliated Hospital of Wannan Medical CollegeYijishan Hospital of Wannan Medical College Institute of Surgery Research Daping HospitalThird Military Medical University

It is of great significance to find safe and effective radiosensitizers. A primary investigation has been made on fisetin's modification of radiation effect, but its radiosensitization and related mechanisms still need to be deeply clarified. Furthermore, fisetin with high hydrophobicity is difficult to dissolve in water,severely limiting its research and application. In this study, we fabricated a safe and soluble radiosensitizer fisetin micelle for precisely enhancing radiotherapy by inhibiting platelet-derived growth factor receptor-β(PDGFRβ)/signal transducer and activator of transcription 1(STAT1)/signal transducer and activator of transcription 3(STAT3)/B cell lymphoma 2(Bcl-2) signaling pathway in the tumor. Systematic and detailed studies were performed to verify its radiosensitization effect in vitro and in vivo. On the cellular level, fisetin micelles selectively increased the radiosensitivity of tumor cells(CT26 and 4T1 cells)and had little effect on the sensitivity of normal mouse cells(L929 cells) to radiation. In the mouse models of colon and breast cancers, fisetin micelles showed an efficient radiosensitization capacity without apparent toxicity. Additionally, we first found that fisetin micelles played a radiotherapy sensitization role by inhibiting the PDGFRβ/STAT1/STAT3/Bcl-2 pathway activity. In general, this work not only confirmed that fisetin micelles precisely exhibit a radiosensitization effect in vitro and in vivo, but also profoundly explored its mechanisms underlying, to provide a theoretical and experimental basis for the clinical application of fisetin micelles.

关键词： Fisetin Platelet-derived growth factor receptor-β Polymetric micelles Radiosensitizer Radiotherapy

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Composite score of PD-1+CD8+ tumor-infiltrating lymphocytes and CD57+CD8+ tumor ascites lymphocytes is associated with prognosis and tumor immune microenvironment of patients with advanced high-grade serous ovarian cancer

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Chinese Journal of Cancer Research 2025年第01期 73-99页

作者： Tianhui He Jie Zhang Lin Zeng Zhongnan Yin Bo Yu Xi Zhang Xiaoxue Yang Chunliang Shang Lixiang Xue Hongyan Guo Department of Obstetrics and Gynecology Peking University Third Hospital center of Basic medical Research Institute of Medical Innovation and Research Peking University Third Hospital Biobank Peking University Third Hospital Research center of Clinical Epidemiology Peking University Third Hospital

Objective: The expression of programmed death 1（PD-1） on CD8+T cells is associated with their activation and exhaustion, while CD57 serves as a senescence marker. The impact of PD-1+and CD57+CD8+T cells on the prognosis of patients with advanced high-grade serous ovarian cancer（HGSOC） remain ***: We assessed the percentages of PD-1+and CD57+CD8+T cells in tumor-infiltrating lymphocytes（TILs, n=85） and tumor ascites lymphocytes（TALs, n=87） using flow cytometry. The optimal cutoffs for these markers in TILs and TALs were determined through the log-rank maximization method. Gene expression analysis elucidated the tumor immune microenvironment（TIME, n=36）.Results: Patients with higher PD-1+CD8+TILs（>87.8%） exhibited longer platinum-free interval（PFI） and overall survival（OS）. In contrast, those with elevated CD57+CD8+TALs（>28.69%） were more likely to experience chemotherapy and had lower complete remission rates, shorter PFI and OS. PD-1+CD8+TILs are primarily displayed an effector memory state with strong proliferative and secretory capabilities. Approximately 50% of CD57+CD8+TALs were terminally differentiated, exhibiting significantly impaired proliferation. Based on the proportions of PD-1+CD8+TILs and CD57+CD8+TALs, patients were categorized into good, median and poor prognosis groups, with median PFI of 47.78, 27.29 and 11.96 months, respectively（P<0.0001）. Median OS for these groups was not reach, 49.23 and 30.92 months, respectively（P<0.0001）. Patients with poor prognosis exhibit significantly reduced CD8+T cell proportion and increased M2 macrophage in the TIME, alongside downregulation of multiple T cell activation-related ***: Lower levels of PD-1+CD8+TILs and higher CD57+CD8+TALs, assessed prior to treatment,correlated with poor prognosis and suppressive TIME in advanced HGSOC.

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Xiangshao Granules Ameliorate Post-stroke Depression by Inhibiting Activation of Microglia and IDO1 Expression in Hippocampus and Prefrontal Cortex

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Chinese Journal of Integrative Medicine 2025年第1期31卷 28-38页

作者： LI Cheng-gang XU Lu-shan SUN Liang XU Yu-hao CAO Xiang ZHAO Chen-chen XIA Sheng-nan ZHANG Qing-xiu XU Yun Department of Neurology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases Nanjing UniversityNanjing210008China Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjing210008China Nanjing Neurology medical center Nanjing210008China

Objective To investigate the therapeutic effect of Xiangshao Granules(XSG)on post-stroke depression(PSD)and explore the underlying *** Forty-three C57BL/6J mice were divided into 3 groups:sham(n=15),PSD+vehicle(n=14),and PSD+XSG(n=14)groups according to a random number *** PSD models were constructed using chronic unpredictable mild stress(CUMS)after middle cerebral artery occlusion(MCAO).The sham group only experienced the same surgical operation,but without MACO and CUMS *** XSG group received XSG(60 mg/kg per day)by gavage for 4 *** mice in the sham and vehicle groups were given the same volume of 0.9%saline at the same *** body weight and behavior tests including open field test,sucrose preference test,tail suspension test,and elevated plus-maze test,were used to validate the PSD mouse ***-time fluorescence quantitative polymerase chain reaction(RT-qPCR),enzyme-linked immunosorbent assay(ELISA),and immunofluorescence staining were used to evaluate the anti-inflammatory effects of *** potential molecular mechanisms were explored and verified through network pharmacology analysis,Nissl staining,Western blot,ELISA,and RT-qPCR,*** The body weight and behavior tests showed that MCAO combined with CUMS successfully established the PSD *** alleviated neuronal damage,reduced the expressions of pro-apoptotic proteins Caspase-3 and B-cell lymphoma-2(BCL-2)-associated X(BAX),and increased the expression of anti-apoptotic protein BCL-2 in PSD mice(P<0.05 or P<0.01).XSG inhibited microglial activation and the expressions of pro-inflammatory cytokines including tumor necrosis factor-α,interleukin(IL)-1β,and IL-6 via the toll-like receptor 4/nuclear factor kappa-B signaling pathway in PSD mice(P<0.05 or P<0.01).Furthermore,XSG decreased the expression of indoleamine 2,3-dioxygenase1(IDO1)and increased the concentration of 5-hydroxytryptamine in PSD mice(P<0.05 or P<0.01).Conclusion XSG could reverse

关键词： post-stroke depression Xiangshao Granules indoleamine 2,3-dioxygenase 1 Chinese medicine

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Multicenter analysis on the correlation between the anatomical characteristics of hepatic veins and hepatic venous wedge pressure

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World Journal of Gastroenterology 2025年第9期31卷 43-53页

作者： Qiu-Xia Ye Ming-Ming Meng Yi-Fan Wu Cheng-Bin Dong Yu Zhang Bo-Wen Liu Yi-Fan Lv Shao-Li You Sa Lv Hui-Guo Ding Ying Han Yong-Ping Yang Bing Zhu Fu-Quan Liu Liver Disease Minimally Invasive Diagnosis and Treatment center Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China Liver Vascular Disease Diagnosis and Treatment center The Fifth Medical Center of Chinese People's Liberation Army General HospitalBeijing 100039China Department of Gastroenterology and Hepatology Beijing You’an HospitalCapital Medical UniversityBeijing 100069China

BACKGROUND Wedged hepatic venous pressure(WHVP)is a crucial variable for accurately assessing the hepatic venous pressure gradient(HVPG)and is vital for the diagnosis and prognostic evaluation of patients with portal hypertension(PH).AIM To investigate the anatomical characteristics of balloon-occluded hepatic venous angiography in patients with PH and analyze the relationship between the WHVP and portal venous pressure(PVP).METHODS This retrospective study included 877 patients with PH who met the inclusion criteria from January 2020 to June *** and innovative hepatic venous angiography was performed during transjugular intrahepatic portosystemic shunt procedures to measure hepatic venous and *** patients'angiographic images were collected for *** associations between WHVP and PVP in each group were analyzed via linear regression analysis,and a predictive model was *** The 877 patients had a mean age of 52.6±13.0 years,with 582 males and 295 *** were categorized into four groups on the basis of their anatomical *** groups showed strong correlations between WHVP and *** regression coefficient between the WHVP and PVP in the hepatic right vein-portal venous angiography group was 0.884(P<0.05);in the hepatic right vein-accessory hepatic venous angiography group,it was 0.721(P<0.05);in the hepatic right vein-middle hepatic venous angiography group,it was 0.344(P<0.05);and in the hepatic right vein-nonangiography group,it was 0.293(P<0.05).CONCLUSION The presence and anatomical classification of hepatic venous collaterals are key factors influencing the relationship between WHVP with and *** on the different anatomical classifications of hepatic veins,WHVP can be used to estimate PVP,improving the accuracy of PVP prediction.

关键词： Wedged hepatic venous pressure Portal venous pressure Portal hypertension Collateral branches of the hepatic vein Transjugular intrahepatic portosystemic shunt

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Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

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Neural Regeneration Research 2025年第8期20卷 2373-2381页

作者： Lifang Zhao Mingkai Zhang Qimeng Li Xuemin Wang Jie Lu Ying Han Yanning Cai Department of Clinical Biobank Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Geriatric medical Research center BeijingChina Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Radiology and Nuclear Medicine Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics BeijingChina Key Laboratory of Neurodegenerative diseases Ministry of EducationBeijingChina School of Biomedical Engineering Hainan UniversityHaikouHainan ProvinceChina center of Alzheimer’s Disease Beijing Institute for Brain DisordersBeijingChina National Clinical Research center for Geriatric Diseases BeijingChina Institute of Biomedical Engineering Shenzhen Bay LaboratoryGaoke Innovation CenterShenzhenGuangdong ProvinceChina Department of Neurobiology Xuanwu HospitalCapital Medical UniversityBeijingChina

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative ***,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°*** aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large *** samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline *** samples were stored at-80°C for up to 6 years before being used in this *** results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage ***,the level of total tau showed a negative correlation with sample storage ***,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage *** was not observed in individuals with cognitive ***,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage ***,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's ***,in cohort studies,it is important to consider the impact of storage time on the overall results.

关键词： Alzheimer’s disease amyloid-β diagnostic ability glial fibrillary acidic protein neurodegeneration neurofilament light chain plasma biomarkers single molecule array storage time tau

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Intratumoral injection of two dosage forms of paclitaxel nanoparticles combined with photothermal therapy for breast cancer

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Chinese Herbal Medicines 2025年第1期17卷 156-165页

作者： Lina Sun Cuiling Zuo Baonan Ma Xinxin Liu Yifei Guo Xiangtao Wang Meihua Han Institute of Medicinal Plant Development Chinese Academy of Medical Sciences & Peking Union Medical College Research center of Pharmaceutical Engineering Technology Harbin University of Commerce

Objective:In order to enhance the efficacy of anti-breast cancer,paclitaxel nanoparticles（PTX NPs） and polypyrrole nanoparticles（PPy NPs） were combined with photothermal therapy and *** the same time,the two dosage forms of PTX NPs and PTX NPs gel were ***:PTX NPs were prepared by self-assembly method,and then the cytotoxicity in vitro was investigated by Methyl thiazolyl tetrazolium（MTT） and other methods,and the efficacy and side effects in vivo were further ***:The average hydrated diameter,PDI and electric potential of PTX NPs were（210.20±1.57） nm,（0.081±0.003） mV and（15.80±0.35） mV,*** results showed that the IC50value of PTX NPs on 4 T1 cells was 0.490 μg/mL,while that of PTX injection was 1.737 μg/*** cell inhibitory effect of PTX NPs was about 3.5 times higher than that of PTX *** tumor inhibition rates of PTX NPs and gel were 48.64% and 56.79%,*** with local photothermal stimulation,the tumor inhibition rate of the PTX NPs reached 91.05%,surpassing that of the gel under the same conditions（48.98%）,moreover,the organ index and H&E staining results of PTX NPs showed a decrease in ***:This combination therapy can significantly enhance the effect of anti-breast cancer,and the synergistic effect of chemotherapy and light and heat provides a feasible and effective strategy for the treatment of tumor.

关键词： breast cancer combination therapy paclitaxel photothermal therapy polypyrrole

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Pyroptosis,ferroptosis,and autophagy in spinal cord injury:regulatory mechanisms and therapeutic targets

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Neural Regeneration Research 2025年第10期20卷 2787-2806页

作者： Qingcong Zheng Du Wang Rongjie Lin Weihong Xu Department of Spinal Surgery the First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Arthritis Clinical and Research center Peking University People’s HospitalBeijingChina Department of Orthopedic Surgery Fujian Medical University Union HospitalFuzhouFujian ProvinceChina

Regulated cell death is a form of cell death that is actively controlled by *** studies have shown that regulated cell death plays a key role after spinal cord *** and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal ***,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord *** injury triggers not only cell death but also cellular survival *** signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and ***,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord *** analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord ***,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.

关键词： autophagy cell death ferroptosis inflammation pathological mechanisms pyroptosis regulated cell death regulatory pathways spinal cord injury therapeutic targets

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DTD1 modulates synaptic efficacy by maintaining D-serine and D-aspartate homeostasis

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Science China(Life Sciences) 2025年第2期68卷 467-483页

作者： Xiao Liu Chaojuan Yang Zhuoran Lin Jianing Li Bin Yin Xuepei Lei Wei Han Boqin Qiang Pengcheng Shu Chen Zhang Xiaozhong Peng State KeyLaboratoryofCommon Mechanism Research for Major Diseases Departmentof Biochemistry&Molecular BiologyMedicalPrimate Research CenterNeuroscienceCenterInstituteof Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China State Key Laboratory of Respiratory Health and Multimorbidity Beijing 100005China Institute of Laboratory Animal Sciences Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China School of Basic medical Sciences Beijing Key Laboratory of Neural Regeneration and RepairCapital Medical UniversityBeijing 100069China Key Laboratoryof Biomechanics and Mechanobiology(Beihang university) Ministryof EducationBeijing AdvancedInnovation Center for Biomedical EngineeringSchoolof Engineering MedicineBeihang UniversityBeijing 100191China Chinese Institute for Brain Research Beijing 102206China

D-serine and D-aspartate are involved in N-methyl-D-aspartate receptor(NMDAR)-related physiological and pathological ***-t RNA deacylase 1(DTD1)may biochemically contribute to D-serine or D-aspartate ***,it is unclear thus far whether DTD1 regulates D-serine or D-aspartate content in neurobiological *** the present research,we found that DTD1 was essential to maintain the D-serine or D-aspartate homeostasis,which was consistent with the phenomenon that DTD1-deficiency resulted in changes in the quantity changes of functional NMDAR subunits in postsynaptic ***,DTD1 played a considerable role in regulating dendritic morphology and synaptic *** a consequence,DTD1 affected neurobiological events,including the synaptic strength of the CA3-to-CA1 circuit,dendritic spine density of hippocampal pyramidal neurons,and behavioral performance of mice in the Morris water *** findings highlight the important role of DTD1 in synaptic transmission,neuronal morphology,and spatial learning and memory and suggest an undisclosed mechanism of DTD1 that participates the regulation of D-serine or D-aspartate homeostasis in hippocampal neurons.

关键词： D-aminoacyl-tRNA deacylase 1 D-serine D-aspartate synaptic transmission neuronal morphology spatial learning and memory

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Adaptive neoadjuvant endocrine therapy screens out prime population of ribociclib intensive adjuvant therapy

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Chinese Journal of Cancer Research 2025年第01期 115-117页

作者： Zhao Bi Tongyue Ren Yongsheng Wang Breast Cancer center Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences

The latest data from the NATALEE trial showed the absolute 3-year invasive disease-free survival benefit was 4.9% between the experimental and control groups. That is to say, in the intermediate-risk hormone receptor positive/human epidermal growth factor receptor-2 negative subgroup, there are also some patients with primary resistance to ribociclib. These patients benefit less from ribociclib, and they are unable to gain significant benefit even with the intensive adjuvant therapy of ribociclib. Considering the drug toxicity and health economic benefits, a 3-year course of ribociclib may not be appropriate for all intermediate-risk populations. Therefore, how to screen out the prime population for intensive adjuvant therapy of ribociclib needs to worth explored. In this paper, we discussed that the adaptive neoadjuvant endocrine therapy can screen out the prime population for intensive adjuvant therapy of ribociclib.

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Advances in gastrointestinal vascular bleeding disorders:Successful sirolimus treatment in colonic angioectasia

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World Journal of Gastroenterology 2025年第4期31卷 123-136页

作者： Qi Sun Xiao-Ying Wang Dong-Hao Li Bai-Rong Li Xin-Zhuo Tu Zhi-Meng Jiang Shou-Bin Ning Tao Sun Department of Gastroenterology Air Force Medical CenterBeijing 100142China College of Life Science Northwest UniversityXi’an 710069Shaanxi ProvinceChina Department of Pathology Air Force Medical CenterBeijing 100142China

BACKGROUND Gastrointestinal(GI)vascular bleeding disorders pose significant clinical challenges due to their complex pathogenesis and varied treatment *** advancements in diagnostic and therapeutic techniques,optimal mana-gement strategies remain elusive,necessitating further *** To assess research trends and clinical advancements in GI vascular bleeding disorders,highlighting key themes and therapeutic *** A bibliometric analysis was conducted using the Web of Science Core Collection database,reviewing publications from 2000 to 2024 to identify trends,highfrequency keywords,and key contributions from leading research *** addition,a case study highlighted the effective application of sirolimus in managing colonic angioectasia in a patient with recurrent GI bleeding who had not responded to previous *** The analysis reviewed 470 scholarly articles from 203 countries,involving 2817 authors across 1502 *** United States led in publication contributions,with strong collaborations with countries like China,England,and Germany.A significant trend was observed in the shift from traditional endoscopic interventions to pharmacological therapies,particularly highlighting the successful use of sirolimus in treating colonic angioectasia. High-frequency keywords such as “angiodysplasia”,“colon”, and “management” were identified, indicating key research themes. The study also noted a growinginterest in drug therapies, as evidenced by the increasing prominence of keywords like “thalidomide” since *** study links bibliometric analysis and clinical insights, highlighting the shift to pharmacological managementin GI vascular bleeding disorders to improve patient outcomes.

关键词： Gastrointestinal bleeding Vascular anomalies Angioectasia Pharmacological Sirolimus

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