Journal of Sun Yat-sen University (Medical Sciences)

Journal of Sun Yat-sen University (Medical Sciences)Journal of Sun Yat-sen University (Medical Sciences)

Editor-in-Chief:GAO Guoquan

ISSN:1672-3554

CN:44-1575/R

Supervisor:the Ministry of Education of China

Sponsor:Sun Yat-sen University

Publication frequency:Bimonthly

Tel.:020-87331643

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Volume 47  Issue 5，2026

  • Review

      ABDUGHENI·Karima, LIU Junxiu

      DOI：10.11714/jsysu.med.YX20260120
      Abstract：Epithelial ovarian cancer （EOC）， particularly high-grade serous ovarian cancer （HGSOC）， commonly presents with intraperitoneal dissemination， peritoneal implants， and malignant ascites. The objective response rate to immune checkpoint inhibitor （ICI） monotherapy is approximately 8%-15%. A key underlying reason is that the distinctive intraperitoneal spread of EOC places tumor cells simultaneously within both a “solid” microenvironment （formed by solid lesions/peritoneal implants） and a “liquid” microenvironment （represented by malignant ascites）； these two compartments continuously interact through cellular trafficking， exosome-mediated transfer， cytokine diffusion， and lipid metabolic exchange， collectively shaping the typical “cold tumor” phenotype. Centered on this solid-liquid dual microenvironment， this review dissects， at the cellular level， the immunosuppressive network established by M2-polarized tumor-associated macrophages， enriched regulatory T cells， expanded myeloid-derived suppressor cells， and dysfunctional dendritic/NK and CD8+ T cells； and elucidates， at the molecular level， the central roles of IL-4/IL-6/TGF-β/VEGF cytokine axis imbalance， lipid metabolic reprogramming， lactate accumulation， and impaired antigen presentation in driving T-cell exhaustion and platinum resistance. On the therapeutic front， integrating the latest evidence from KEYNOTE-B96， DUO-O， FIRST/ENGOT-OV44， ATHENA-COMBO， MIRASOL， OVHIPEC-1 and PIPAC studies， this review summarizes the evidence supporting immune-combination regimens， anti-angiogenic agents， folate receptor alpha antibody-drug conjugates， hyperthermic intraperitoneal chemotherapy， and local intraperitoneal delivery from the dual perspectives of systemic immune modulation and local microenvironment intervention. The dual-microenvironment framework may help explain the poor response to immunotherapy and inform rational combination strategies in EOC； however， clinical translation should be based on precise stratification according to histology， BRCA/homologous recombination deficiency status， PD-L1 and folate receptor alpha expression， and spatial immune phenotypes.  
      Keywords：ovarian cancer;tumor microenvironment;ascites;immune evasion;immune checkpoint inhibitors  
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      Updated：2026-09-20

      • ZHENG Na, AN Hongwei

        DOI：10.11714/jsysu.med.YX20260093
        Abstract：Multiple sclerosis （MS） is a chronic immune-mediated demyelinating disease of the central nervous system. As the resident innate immune cells of the CNS， microglia exert dual regulatory effects throughout the disease course， encompassing both detrimental and reparative functions. Numerous studies have confirmed that microglia exhibit significant heterogeneity across development， aging， and pathological states， and multiple subpopulations have been identified， including proliferative region-associated microglia， disease-associated microglia， interferon-responsive microglia， and microglia inflamed in MS. This review summarizes the current state of microglial heterogeneity research and its implications in MS， with a particular focus on the mechanisms underlying their regulation of neuroinflammation and remyelination. It provides a theoretical reference for precision therapies targeting microglial subpopulations and offers novel insights for the clinical management of MS.  
        Keywords：multiple sclerosis;microglia;heterogeneity;neuroinflammation;remyelination  
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        Updated：2026-09-20

        • ZHANG Qing, LI Haiyan

          DOI：10.11714/jsysu.med.YX20260077
          Abstract：The incidence of chronic metabolic diseases， including obesity， type 2 diabetes mellitus （T2DM） and metabolic dysfunction-associated steatotic liver disease （MASLD）， continues to rise globally. Disordered glucose and lipid metabolism represents their common pathophysiological foundation. Secreted fibroblast growth factor （FGF） is key regulators of glucose and lipid homeostasis. Among them， the paracrine FGFs， mainly comprising FGF1， FGF2， FGF4， FGF6， FGF8， FGF9， FGF10， and FGF16， require systematic integration regarding their metabolic regulatory functions. This review elucidates the molecular structural characteristics of paracrine FGFs and their central regulatory roles in maintaining glucose and lipid homeostasis， covering their modulation of metabolic networks over multiple tissues and organs including， adipose tissue， liver， skeletal muscle， pancreatic islets， and the nervous system. Furthermore， the expression alterations and functional abnormalities of these factors in chronic metabolic diseases are summarized. This review aims to highlight the critical position of paracrine FGFs in the pathogenesis of metabolic diseases and to provide novel therapeutic targets and theoretical foundations for the prevention and treatment of disorders associated with glucolipid metabolic dysregulation.  
          Keywords：chronic metabolic diseases;glucose and lipid metabolic disorders;paracrine fibroblast growth factors;pathogenesis;therapeutic target  
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          Updated：2026-09-20

          • LI Yonghao, LIU Jiangyan

            DOI：10.11714/jsysu.med.YX20260102
            Abstract：Integrin αvβ3 is an important target for tumor imaging and therapy. It is highly expressed on tumor neovascular endothelial cells and various malignant tumor cells， while being nearly absent in normal tissues and quiescent endothelial cells. Positron emission tomography （PET） based on Arg-Gly-Asp （RGD） peptides has been widely applied， yet single-target strategies are limited by tumor heterogeneity. β- radionuclide-labeled RGD peptides exhibit problems of insufficient tumor uptake and renal accumulation. This review summarizes the preclinical progress in two frontier directions. Dual-targeting strategies combine integrin αvβ3 with prostate-specific membrane antigen （PSMA） or fibroblast activation protein （FAP） to construct heterodimeric probes. Preclinical and clinical studies have demonstrated that dual-targeting probes achieve significantly superior tumor uptake， target-to-background ratios， and lesion detection rates compared to single-target controls， effectively overcoming tumor heterogeneity and improving tumor uptake and detection rate. α radionuclides， by leveraging high linear energy transfer and short tissue range， demonstrate superior antitumor efficacy over β-radionuclides. In terms of clinical translation， the albumin-binding RGD dimer labeled with lutetium-177 （¹⁷⁷Lu-AB-3PRGD₂） has completed a first-in-human study， preliminarily validating the clinical feasibility of integrin-targeted radionuclide therapy， albeit with limited antitumor activity. Future directions include molecular imaging-based patient selection， optimization of dual-targeting molecular structures， and development of α radionuclide formulations.  
            Keywords：integrin αvβ3;radionuclide therapy;dual-targeting strategy;α radionuclides;cancer theranostics  
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            Updated：2026-09-20
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