Seminars in nuclear medicine最新文献

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Corrigendum to ‘18F-FDG PET for Dementia Evaluation: Co-pathologies, New Diseases, and Its Roles in The Era of Anti-Amyloid Treatment’ [Seminar in Nuclear Medicine volume 55 (2025):526 –537/Article number YSNUC_51208] “18F-FDG PET用于痴呆评估：共病理，新疾病及其在抗淀粉样蛋白治疗时代的作用”的勘误表[核医学研讨会卷55(2025):526 -537/文章编号YSNUC_51208]。

IF 5.9 2区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Seminars in nuclear medicine

Pub Date : 2025-09-25 DOI: 10.1053/j.semnuclmed.2025.09.001

Tanyaluck Thientunyakit , Weerasak Muangpaisan , Satoshi Minoshima

引用次数: 0

Expanding the Horizon of Targeted Radionuclide Therapy: Immunotherapy Combinations and FAP-Targeted Approaches 扩大靶向放射性核素治疗的视野：免疫治疗组合和fap靶向方法。

IF 5.9 2区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Seminars in nuclear medicine

Pub Date : 2025-09-22 DOI: 10.1053/j.semnuclmed.2025.08.003

Ayça Arçay Öztürk, Wendy Delbart, Patrick Flamen

Targeted radionuclide therapy (TRT) has emerged as a promising cancer treatment modality and is increasingly recognized as an immunomodulatory tool, similar to external beam radiotherapy (EBRT). Both forms of radiation can reshape the tumor immune microenvironment, providing a rationale for their combination with immune checkpoint inhibitors (ICIs) to harness synergistic effects while mitigating immunosuppressive mechanisms. Outcomes of such combinations depend on radiation dose/fractionation, treatment sequencing, target selection, and the choice of immunotherapeutic/radiopharmaceutical agents. Among novel TRT strategies, fibroblast activation protein-TRT (FAP-TRT) stands out for its targeting of cancer-associated fibroblasts (CAFs), key components of the tumor stroma involved in immune evasion and therapy resistance. Unlike conventional TRTs that directly target tumor cells, FAP-TRT acts on CAFs, potentially modulating the tumor microenvironment to enhance the immunomodulatory effects of radiation. This review examines the immunological effects of radiation—via EBRT or TRT-and the rationale for combining TRT with ICIs. We highlight preclinical and clinical studies demonstrating both the synergistic potential and context-specific limitations of TRT–ICI combinations. Emphasis is placed on the emerging role of FAP-TRT in remodeling the tumor microenvironment, converting “cold” tumors into “hot” phenotypes, and enhancing immune infiltration. Preclinical models show synergy between FAP-TRT and ICIs, but challenges remain, including clarifying FAP-TRT’s effects on CAF subpopulations, optimizing radiopharmaceutical design, and addressing shared issues with TRT/EBRT–ICI combinations, such as dosing, sequencing, and target selection. The integration of TRT and immunotherapy—particularly FAP-TRT combinations—offers a compelling avenue for precision oncology and warrants further translational and clinical investigation.

靶向放射性核素治疗（TRT）已成为一种很有前景的癌症治疗方式，并越来越被认为是一种免疫调节工具，类似于外部放射治疗（EBRT）。这两种形式的辐射都可以重塑肿瘤免疫微环境，为它们与免疫检查点抑制剂（ICIs）联合使用提供了基本原理，以利用协同效应，同时减轻免疫抑制机制。这种组合的结果取决于辐射剂量/分离、治疗顺序、靶点选择和免疫治疗/放射药物的选择。在新的TRT策略中，成纤维细胞活化蛋白-TRT （FAP-TRT）因其靶向癌症相关成纤维细胞（CAFs）而脱颖而出，CAFs是肿瘤基质中参与免疫逃避和治疗抵抗的关键成分。与直接靶向肿瘤细胞的传统trt不同，FAP-TRT作用于CAFs，可能调节肿瘤微环境以增强辐射的免疫调节作用。本文综述了辐射（通过EBRT或TRT）的免疫效应，以及TRT联合ICIs的基本原理。我们强调临床前和临床研究证明了TRT-ICI联合的协同潜力和具体情况的局限性。重点介绍了FAP-TRT在重塑肿瘤微环境、将“冷”型肿瘤转化为“热”型、增强免疫浸润等方面的新作用。临床前模型显示了FAP-TRT和ICIs之间的协同作用，但挑战仍然存在，包括澄清FAP-TRT对CAF亚群的影响，优化放射性药物设计，以及解决TRT/EBRT-ICI组合的共同问题，如剂量，测序和靶标选择。TRT和免疫治疗的结合，特别是FAP-TRT联合治疗，为精确肿瘤学提供了一条令人信服的途径，值得进一步的转化和临床研究。

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引用次数: 0

CD70-Targeted Radiotheranostics: Now and Future cd70靶向放射治疗：现在与未来。

IF 5.9 2区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Seminars in nuclear medicine

Pub Date : 2025-09-18 DOI: 10.1053/j.semnuclmed.2025.08.001

Binyu Shi , Xinyuan Zhou , Junjun Zhou , Gang Huang , Jianjun Liu , Jin Zhang , Weijun Wei

The cluster of differentiation 70 (CD70), a transmembrane glycoprotein encoded by TNFSF7, is a member of the tumor necrosis factor (TNF) superfamily and serves as the ligand for the co-stimulatory receptor CD27. It is aberrantly overexpressed in various malignancies, including clear cell renal cell carcinoma (ccRCC) and nasopharyngeal carcinoma (NPC). Although CD70-directed radiotheranostics may address key challenges faced by antibody-drug conjugates (ADCs) and chimeric antigen receptor T (CAR-T) therapies, such as drug resistance and tumor penetration barriers, this therapeutic approach remains unexplored in clinical settings. In this review, we highlight the expression of CD70 in normal tissues and organs, as well as in different tumor types, presenting promising results from CD70-targeted immuno-PET/CT imaging in recent clinical trials. Furthermore, we emphasize relevant therapeutic radiopharmaceuticals currently in preclinical or clinical trials, providing a rational roadmap for guiding future development of CD70-targeted radiotheranostics.

分化簇70 （CD70）是一种由TNFSF7编码的跨膜糖蛋白，是肿瘤坏死因子（TNF）超家族的成员，并作为共刺激受体CD27的配体。它在各种恶性肿瘤中异常过表达，包括透明细胞肾细胞癌（ccRCC）和鼻咽癌（NPC）。尽管cd70定向放射治疗可能解决抗体-药物偶联物（adc）和嵌合抗原受体T （CAR-T）疗法面临的关键挑战，如耐药性和肿瘤穿透屏障，但这种治疗方法在临床环境中仍未被探索。在这篇综述中，我们重点介绍了CD70在正常组织和器官以及不同肿瘤类型中的表达，并在最近的临床试验中展示了CD70靶向免疫pet /CT成像的令人鼓舞的结果。此外，我们还重点介绍了目前处于临床前或临床试验阶段的相关治疗性放射药物，为指导cd70靶向放射治疗学的未来发展提供了合理的路线图。

引用次数: 0

Radiolabeled Antibody–Drug Conjugates in the Treatment of Solid Tumors 放射标记抗体-药物偶联物在实体肿瘤治疗中的应用。

IF 5.9 2区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Seminars in nuclear medicine

Pub Date : 2025-09-12 DOI: 10.1053/j.semnuclmed.2025.08.002

Ismaheel O. Lawal , Sofiullah Abubakar , Honest Ndlovu , Aisha Ismaila , Mike M. Sathekge

Antibody-drug conjugates (ADCs) utilize monoclonal antibodies (mAbs) that target tumor-specific antigens to deliver potent cytotoxic chemotherapy payloads to the tumor, while sparing normal tissues. The chemotherapy agents employed in ADCs are very potent, causing a tumoricidal effect at low drug concentrations. Several ADCs have been approved for the treatment of different solid tumors over the last decade following the superior efficacy and safety they demonstrated above standard-of-care treatment modalities in several clinical trials. Despite their efficacy, some patients do not respond to treatment with ADCs, as objective response rate typically range from 30% to 50%, and as low as 20% in some instances. Some patients who initially respond to treatment develop acquired resistance during their treatment, necessitating strategies to improve response rates and overcome treatment resistance. Radiation from radionuclides, with their ability to evoke a synergistic antitumor effect when used in combination with cytotoxic chemotherapy and induce a tumoricidal effect in tumor cells remote from the tumor they are bound to (crossfire effect), has the potential to improve the outcomes of ADC treatment. An expanding body of evidence, reporting the successful radiolabeling of established and experimental ADCs, is emerging in the literature. These studies have demonstrated improved antitumor effect of radiolabeled ADC relative to cold ADC, paving the way for further exploration, including in clinical settings.

抗体-药物偶联物（adc）利用针对肿瘤特异性抗原的单克隆抗体（mab）向肿瘤提供有效的细胞毒性化疗有效载荷，同时不影响正常组织。adc中使用的化疗药物非常有效，在低药物浓度下就能产生杀瘤作用。在过去的十年中，几种adc已被批准用于治疗不同的实体肿瘤，因为它们在几项临床试验中显示出优于标准治疗模式的疗效和安全性。尽管adc有疗效，但一些患者对其治疗没有反应，因为客观反应率通常在30%至50%之间，在某些情况下低至20%。一些最初对治疗有反应的患者在治疗期间出现了获得性耐药，需要采取策略来提高反应率并克服治疗耐药。放射性核素的辐射在与细胞毒性化疗联合使用时能够引起协同抗肿瘤作用，并在远离其所结合肿瘤的肿瘤细胞中诱导杀瘤作用（交叉火力效应），具有改善ADC治疗结果的潜力。文献中出现了越来越多的证据，报告了已建立的和实验性adc的成功放射性标签。这些研究表明，放射性标记ADC的抗肿瘤效果优于冷ADC，为进一步探索铺平了道路，包括在临床环境中。

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引用次数: 0

Implementation of Radiotheranostics: Challenges, Barriers, and IAEA-Driven Strategies for Sustainable Access 放射肿瘤学的实施：挑战、障碍和原子能机构驱动的可持续获取战略。

IF 5.9 2区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Seminars in nuclear medicine

Pub Date : 2025-08-31 DOI: 10.1053/j.semnuclmed.2025.07.005

Akram Al-Ibraheem , Anita Brink , Sze Ting Lee , Amelia De Los Reyes , Diana Paez , Pietro Selemo Craviolatti , Augusto Llamas-Olier , Francesco Giammarile , Ahmed S. Abdlkadir , Enrique Estrada-Lobato , May Abdel-Wahab , John Prior , Andrew M. Scott , Mike Machaba Sathekge

Radiotheranostics represent a cutting-edge advancement in the management of noncommunicable diseases, integrating diagnostic imaging with targeted radiotherapy in a single, personalized approach. Over the past decade, the field has gained substantial momentum, with several radiopharmaceuticals now incorporated into clinical practice, most notably for neuroendocrine tumors and prostate cancer. The pipeline of novel agents continues to grow, offering promising therapeutic options for patients with cancers resistant to conventional therapies. Despite these advances, the broad implementation of radiotheranostics is impeded by several challenges, including logistical constraints, financial limitations, resource scarcity, political instability, and regulatory and educational barriers. Overcoming these obstacles requires coordinated mitigation strategies focused on strengthening education and training, expanding radiopharmaceutical production and development, enhancing research capacity, and establishing robust quality management systems. This review provides a comprehensive overview of the current global landscape of radiotheranostics, identifies key implementation barriers, and offers expert-driven strategies and recommendations from the International Atomic Energy Agency to support sustainable and equitable access to radiotheranostics.

放射肿瘤学代表了非传染性疾病管理的前沿进展，将诊断成像与靶向放疗以单一的个性化方法相结合。在过去的十年中，该领域获得了巨大的发展势头，一些放射性药物现已纳入临床实践，最明显的是用于神经内分泌肿瘤和前列腺癌。新型药物的研发渠道持续增长，为那些对传统疗法有耐药性的癌症患者提供了有希望的治疗选择。尽管取得了这些进展，但放射治疗的广泛实施仍受到一些挑战的阻碍，包括后勤限制、财政限制、资源稀缺、政治不稳定以及监管和教育障碍。克服这些障碍需要协调一致的缓解战略，重点是加强教育和培训，扩大放射性药物的生产和开发，提高研究能力，建立健全的质量管理体系。本综述全面概述了当前全球放射治疗的概况，确定了关键的实施障碍，并提供了专家驱动的战略和国际原子能机构的建议，以支持可持续和公平地获得放射治疗。

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引用次数: 0

GRPR Expression in Metastatic Cancers: A Review of Potential Application of GRPR-Radioligand Therapy GRPR在转移性癌症中的表达：GRPR放射配体治疗的潜在应用综述。

IF 5.9 2区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Seminars in nuclear medicine

Pub Date : 2025-08-11 DOI: 10.1053/j.semnuclmed.2025.07.003

Aurélien Callaud , Heying Duan , Elif Hindié , Clément Morgat , Andrei Iagaru

Gastrin-Releasing Peptide Receptor (GRPR) represents a promising molecular target for radionuclide therapy (TRT) across a variety of malignancies due to its overexpression in several tumor types, including prostate, breast, lung, melanoma, cervix, neuroblastoma, head and neck, and colon cancers. While expression patterns vary—with high GRPR expression notably observed in cervix and neuroblastoma cancers—tumor heterogeneity and metastatic profiles remain challenges for patient selection and therapy optimization. Recent advances in GRPR-targeted radiopharmaceutical development have focused on overcoming peptide instability and enhancing tumor uptake, exemplified by novel compounds such as AMTG with improved proteolytic resistance and albumin binding domains to extend circulatory half-life. Furthermore, innovative radionuclides like terbium-161, lead-212, copper-67, cobalt-58 m, and arsenic-77 offer enhanced therapeutic potential beyond the current standard of lutetium-177 through favorable decay characteristics including Auger electron emission and alpha-particle therapy. Preclinical and early clinical studies demonstrate encouraging tumor targeting and therapeutic efficacy with manageable toxicity profiles, particularly in prostate and cervix cancers. However, further investigation into GRPR expression heterogeneity, metastatic distribution, and safety is necessary to refine patient stratification and maximize clinical benefit. This evolving landscape positions GRPR-TRT as a versatile and potent approach, with the potential to expand targeted radionuclide therapy to a broader range of malignancies and improve outcomes in advanced cancers with limited treatment options.

胃泌素释放肽受体（GRPR）在多种肿瘤中过表达，包括前列腺癌、乳腺癌、肺癌、黑色素瘤、宫颈癌、神经母细胞瘤、头颈癌和结肠癌，是放射性核素治疗（TRT）的一个有希望的分子靶点。虽然表达模式各不相同——在子宫颈和神经母细胞瘤中观察到GRPR的高表达——但肿瘤的异质性和转移特征仍然是患者选择和治疗优化的挑战。grpr靶向放射性药物开发的最新进展集中在克服肽不稳定性和增强肿瘤摄取上，例如AMTG等新型化合物具有改善的蛋白水解抗性和白蛋白结合域，以延长循环半衰期。此外，创新的放射性核素，如铽-161、铅-212、铜-67、钴-58 m和砷-77，通过包括俄热电子发射和α粒子治疗在内的良好衰变特性，提供了比目前标准的镥-177更高的治疗潜力。临床前和早期临床研究证明了令人鼓舞的肿瘤靶向性和治疗效果以及可控的毒性，特别是在前列腺癌和宫颈癌中。然而，进一步研究GRPR的表达异质性、转移分布和安全性对于完善患者分层和最大化临床获益是必要的。这种不断发展的前景使GRPR-TRT成为一种多功能和有效的方法，有可能将靶向放射性核素治疗扩大到更广泛的恶性肿瘤，并改善治疗选择有限的晚期癌症的预后。

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引用次数: 0

The Role of [177Lu] Lu-Satoreotide Tetraxetan in Somatostatin Receptor-Positive Neuroendocrine Tumors [177Lu] Lu-Satoreotide Tetraxetan在生长抑素受体阳性神经内分泌肿瘤中的作用。

IF 5.9 2区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Seminars in nuclear medicine

Pub Date : 2025-08-11 DOI: 10.1053/j.semnuclmed.2025.07.002

Kalyan Mansukhbhai Shekhda , Shaunak Navalkissoor

Peptide receptor radionuclide therapy (PRRT) targeting the somatostatin receptor with receptor agonists has emerged as a key treatment in the management of well-differentiated neuroendocrine tumors (NETs). The therapeutic efficacy of these agents has traditionally been attributed to receptor-mediated internalization of the radiolabeled peptide into tumor cells. In contrast, somatostatin receptor (SSTR) antagonists bind to the receptor without undergoing significant internalization. Despite this theoretical limitation, accumulating preclinical and clinical evidence supports the therapeutic utility of SSTR antagonists. These agents have been shown to bind to a greater number of receptor sites and exhibit prolonged tumor retention, properties that may enhance both imaging sensitivity and therapeutic efficacy. Among the antagonists studied, [¹⁷⁷Lu]Lu-satoreotide tetraxetan is the most extensively investigated to date. In this article, we review both preclinical and clinical data evaluating the efficacy and safety of [¹⁷⁷Lu]Lu-satoreotide tetraxetan in the treatment of neuroendocrine tumors. We also provide a brief overview of other SSTR antagonists currently under investigation.

利用受体激动剂靶向生长抑素受体的肽受体放射性核素治疗（PRRT）已成为治疗分化良好的神经内分泌肿瘤（NETs）的关键治疗方法。这些药物的治疗效果传统上归因于受体介导的放射性标记肽内化到肿瘤细胞中。相反，生长抑素受体（SSTR）拮抗剂与受体结合而不经历显著的内化。尽管存在理论上的局限性，但越来越多的临床前和临床证据支持SSTR拮抗剂的治疗效用。这些药物已被证明可以结合更多的受体位点，并表现出长时间的肿瘤滞留，这些特性可能会提高成像敏感性和治疗效果。在研究的拮抗剂中，Lu-satoreotide tetraxetan是迄今为止研究最广泛的。在本文中，我们回顾了评估[¹⁷⁷Lu]Lu-satoreotide tetraxetan治疗神经内分泌肿瘤的有效性和安全性的临床前和临床数据。我们还简要概述了目前正在研究的其他SSTR拮抗剂。

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引用次数: 0

Letter from the Editors 编辑的信

IF 5.9 2区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Seminars in nuclear medicine

Pub Date : 2025-07-29 DOI: 10.1053/j.semnuclmed.2025.07.004

Kirsten Bouchelouche, M. Michael Sathekge

引用次数: 0

New Promising Targets for Imaging in Infection 新的有希望的感染成像靶点。

IF 5.9 2区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Seminars in nuclear medicine

Pub Date : 2025-07-22 DOI: 10.1053/j.semnuclmed.2025.06.013

Honest Ndlovu , Ismaheel O. Lawal , Kgomotso M.G. Mokoala , Sipho Mdanda , Mike M. Sathekge

The diagnosis of infection is crucial in-patient survival, prevention of prolonged hospitalization and undue morbidity and mortality. This can be achieved using various tools target at the specific microbes or the host immune response components. The most useful tool will be one that diagnoses the specific causative microbe by being able to distinguish sterile inflammation from infection which by itself causes inflammation. This allows timeous institution of the appropriate and effective antimicrobial therapy, effectively reducing the incidence of antimicrobial resistance. Current standard of care diagnostic tools such as inflammatory markers, culture, morphological imaging and molecular imaging tools has specific shortcomings which necessities enlist other tools to complement them. Various targets for infection imaging have been explored and demonstrated variable utilities in the preclinical or clinical settings. This review will discuss the relevant targets in bacteria, fungi and viruses and delve into the promising or novel molecular imaging tools.

感染的诊断是至关重要的住院病人生存，预防长期住院和不当的发病率和死亡率。这可以使用针对特定微生物或宿主免疫反应成分的各种工具来实现。最有用的工具将是通过能够区分无菌炎症和本身引起炎症的感染来诊断特定致病微生物的工具。这使得适当和有效的抗菌素治疗得以及时建立，有效地减少了抗菌素耐药性的发生率。目前的标准护理诊断工具，如炎症标志物、培养、形态成像和分子成像工具有特定的缺点，需要其他工具来补充。感染成像的各种目标已经被探索，并在临床前或临床设置中展示了不同的效用。本文将讨论细菌、真菌和病毒中的相关靶点，并探讨有前途的或新的分子成像工具。

引用次数: 0

PSMA-Targeted Positron Emission Tomography Imaging in Solid Tumors Other Than Prostate Carcinoma: An Update 前列腺癌以外的实体肿瘤的psma靶向正电子发射断层成像：最新进展。

IF 5.9 2区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Seminars in nuclear medicine

Pub Date : 2025-07-19 DOI: 10.1053/j.semnuclmed.2025.06.006

Nozipho Nyakale , Alex Maes , Mike Sathekge , Shaobo Li , Justine Maes , Christophe Van de Wiele

Prostate-specific membrane antigen (PSMA) has been previously shown to be over-expressed on newly formed vessels of a wide variety of solid tumors other than prostate carcinoma. Accordingly, the potential role of PSMA-targeted positron emitting tomography for staging, restaging and prediction of response to PSMA-targeted treatment modalities, including ¹⁷⁷Lu-PSMA-617, in other solid tumor types is being explored. Results derived from currently available studies on the role of PSMA-targeted imaging in solid tumors other than prostate carcinoma are encouraging with amongst others evidence of improved diagnostic accuracy in patients suffering from clear cell renal cell carcinoma and adenoid cystic adenocarcinoma of the salivary gland when compared to standard of care imaging, leading to a change in patient management in a significant number of patients. Furthermore, in hepatocellular carcinoma and glioblastoma, the comparable diagnostic accuracy of PSMA-targeted PET imaging when compared to contrast-enhanced CT and MRI suggest a potential use of PSMA-targeted PET when findings derived from morphological imaging are doubtful. Also, high PSMA-targeted PET-ligand uptake has been identified in iodine refractory thyroid carcinoma lesions as well as in triple negative breast carcinoma, suggesting a potential role for PSMA-targeted therapy in these patient populations. Thus far published results warrant, however, confirmation by larger prospective studies additionally assessing the longitudinal impact on patient outcomes.

前列腺特异性膜抗原（PSMA）已被证明在除前列腺癌以外的多种实体肿瘤的新形成血管上过表达。因此，在其他实体肿瘤类型中，psma靶向正电子发射断层扫描在psma靶向治疗方式（包括177Lu-PSMA-617）的分期、再分期和预测反应方面的潜在作用正在探索中。目前关于psma靶向成像在前列腺癌以外的实体肿瘤中的作用的研究结果令人鼓舞，其中有证据表明，与标准护理成像相比，透明细胞肾细胞癌和涎腺腺样囊性腺癌患者的诊断准确性得到了提高，导致大量患者的患者管理发生了变化。此外，在肝细胞癌和胶质母细胞瘤中，与对比增强CT和MRI相比，psma靶向PET成像的诊断准确性相当，这表明当形态学成像结果值得怀疑时，psma靶向PET可能会被使用。此外，在碘难治性甲状腺癌病变和三阴性乳腺癌中发现了psma靶向pet配体的高摄取，这表明psma靶向治疗在这些患者群体中具有潜在的作用。然而，到目前为止，已发表的结果仍有待更大规模的前瞻性研究的证实，这些研究还评估了对患者预后的纵向影响。

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