In response to the growing importance of space exploration, the objectives of the COSPAR Panel on Exploration (PEX) are to provide high quality, independent science input to support the development of a global space exploration program, to promote space sciences as a key element of this program, to contribute to maximize its scientific return via enhanced international cooperation, and to take action to safeguard the scientific assets of solar system bodies. This paper summarizes the presentations of the two panel sessions at the COSPAR assembly 2024 and identifies the most intensely discussed recent topics of interest or concern for space exploration. These topics include environment stewardship of celestial bodies, space debris, resource utilization, the Moon, Mars, and other celestial bodies that we want to explore with planetary protection measures, preservation of dark and quiet skies, potential atmospheric pollution, space as an independent goal of sustainable development, human spaceflight, agile and affordable space programs, and the early preparation of a new edition of the COSPAR exploration roadmap.
Limited progress in understanding umbilical hernia (UH) pathogenesis stems from scarce genetically stable models. We established a hereditary rat model recapitulating human and livestock UH across phenotypic, histological, and molecular dimensions. Persistent herniation from infancy to adulthood exhibited size-weight correlation in adults (r2 = 0.139, p < 0.01). Histopathology revealed hernial ring fibrosis, linea alba defects, and collagen dysregulation: reduced collagen I (22.5% decrease, p < 0.01) and elevated collagen III (23.0% increase, p < 0.001), confirming ECM imbalance. Microsatellite analysis validated genetic stability (mean heterozygosity = 0.214; PIC = 0.171). Transcriptomics identified 1,031 differentially expressed genes (712↑, 319↓), enriched in ECM remodeling and immune homeostasis. Cross-species comparative analysis of transcriptomic datasets from established porcine models uncovered conserved pathological mechanisms. Validation of key hub genes (CCL2, EGFR, and ITGA3) by qPCR and ELISA implicates potential pathways in collagen disorganization. This homogeneous model bridges translational gaps for etiology and therapy studies.
Diabetic kidney disease (DKD) is significantly impacting both quality of life and survival rates. The Shen-Yan-Fang-Shuai (SYFS) formula is a traditional Chinese medicine (TCM) compound widely used in the clinical treatment of DKD with proven efficacy, though its potential mechanism of action remains unclear. This study attempts to elucidate the therapeutic efficacy, mechanisms of action, and active compounds of the SYFS formula in the treatment of DKD. The components of SYFS formula were identified by UHPLC-MS/MS. Differentially expressed genes (DEGs) and key module genes were selected based on the GEO database to obtain intersection targets. Protein-protein interaction (PPI) network and component-target network were constructed. Machine learning (ML) was employed to screen for hub genes, which were validated through nomogram, immune infiltration analysis, molecular docking and molecular dynamics (MD) simulation. Subsequently, our findings were validated through a combination of transcriptomic sequencing of renal tissue from animal models and real-time quantitative PCR (qPCR) analyses performed on both the animal tissues and HK-2 cells. 154 chemical components and 994 targets were identified in the SYFS formula. Intersection with DEGs and WGCNA module genes identified 39 potential targets. Five hub genes (MMP3, MMP12, PTGES, SST, and DUSP1) were selected through ML and used to construct a nomogram. Multiple immune cell infiltration levels were significantly elevated in DKD, with hub genes showing correlations with specific immune cell types. Molecular docking and MD simulation validated the binding capacity between components of the SYFS formula and key targets. In addition, it has been further verified in animal experiments and cell experiments. The core components of the SYFS formula, including naringenin chalcone, palmatine, oleanonic acid, β-elemonic acid, and Naringenin, likely exert their effects through the MMP3, MMP12, PTGES, SST, and DUSP1 targets. This research offers empirical support for the application of the SYFS formula in DKD, establishing a crucial groundwork for subsequent clinical investigations.
This study aimed to investigate the therapeutic mechanism of red yeast rice extract (RYRE) in high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) through untargeted metabolomics analysis and experimental validation. An untargeted metabolomics analysis based on UHPLC-QTOF/MS was performed to identify differential metabolites in liver tissues. A NAFLD model was established in hamsters by HFD feeding. Forty hamsters were randomly allocated into four groups (n = 10 per group): control (CON), model (MOD), red yeast rice extract (Xuezhikang, XZK), and simvastatin (SVT). Serum levels of lipids (TG, CHO, HDL-C, LDL-C), liver function parameters (ALT, AST, ALB, ALP, γ-GT, TBiL, DBiL, TBA), and inflammatory cytokines (TNF-α, IL-4, IL-1β, TGF-β) were measured by biochemical assays and ELISA. Liver tissues were subjected to Oil Red O, hematoxylin-eosin (HE), and Masson staining for histopathological evaluation. Additionally, qPCR and immunohistochemistry were employed to investigate the underlying signaling pathways. XZK significantly reduced serum levels of DBiL, TBiL, TBA, CHO, TG, and LDL-C, while increasing HDL-C in HFD-fed hamsters. Both XZK and SVT markedly decreased pro-inflammatory cytokines. Untargeted metabolomics identified 135 differential metabolites between the MOD and XZK groups (83 down-regulated, 52 up-regulated), which were primarily involved in carbon metabolism, lipid metabolism, and hormone metabolism. Mechanistically, XZK attenuated the JNK/AP-1/TNF-α signaling pathway, as evidenced by reduced mRNA expression of cFos, cJUN, JAK1/2/3, and TNF-α, along with decreased protein levels of p-JNK, cFos, cJUN, and TNF-α. Notably, the p-cJun/total cJun ratio showed a distinct regulatory pattern, suggesting complex modulation of AP-1 subunit phosphorylation. XZK effectively ameliorates hepatic steatosis, dyslipidemia, and inflammation in HFD-induced NAFLD hamsters. The therapeutic effects are mediated through restoration of metabolic homeostasis and suppression of the JNK/AP-1/TNF-α signaling pathway.
To synthesize randomized evidence on the effect of cognitive-behavioral therapy (CBT) on anxiety symptoms in individuals with attention-deficit/hyperactivity disorder (ADHD), and to explore whether intervention dose parameters moderate effects. A PRISMA-guided systematic review searched PubMed, Web of Science, PsycINFO, and the Cochrane Library to June 15, 2025. Multilevel random-effects models pooled Hedges' g, and subgroup/meta-regression analyses examined the effects of comparator type and intervention dose. Thirteen RCTs (n = 744). Relative to control conditions, CBT-based interventions reduced anxiety at post-treatment (t(10.00) = -2.97, SMD = -0.29, 95% CI -0.52 to -0.06, P = 0.014) and follow-up (t(6.34) = -4.40, SMD = -0.42, 95% CI -0.71 to -0.13, P = 0.004). Effects were more apparent in adults; pediatric evidence was sparse. Exploratory nonlinear dose-response analyses suggested more favorable estimated effects around 2 sessions/week, ∼50 min/session, over ∼6 weeks (∼5-9 total hours), although these study-level associations should be interpreted cautiously. CBT-based interventions were associated with small-to-moderate reductions in anxiety relative to control conditions in individuals with ADHD, sustained into follow-up. Future large RCTs and meta-analyses should test dose-related hypotheses and evaluate comparative specificity against other bona fide psychotherapies and medication management.
Occupational stress triggers psychological/physical health issues, elevating the risk of burnout and depression. This study explored the interrelationships among these constructs via network analysis (undirected/directed graphs). A total of 1363 participants from Beijing hospitals and a university completed House and Rizzo's Work Stress Scale, Zung's Self-Report Depression Scale, and Maslach Burnout Inventory-General Survey. Graphical Gaussian Model and directed acyclic graphs (DAG) identified core/bridge/upstream nodes and causal pathways. Emotional exhaustion (EE) was the core node (expected influence = 2.11). The strongest edge was D11-D12 (weight = 0.46). EE, occupational stress 11, cynicism (CY), and personal accomplishment (PA) served as key bridging nodes. The network showed high stability (0.75). DAG identified upstream occupational stress 1/7/8, confirming direct occupational stress to depression pathways (emotional dysregulation model) and CY/PA mediated pathways (burnout structural theory). Targeted interventions on core/bridge/upstream nodes may prevent depression onset and progression in occupational settings.
Breast cancer is a prevalent malignancy among women worldwide. Understanding its molecular mechanisms is crucial for prevention, early diagnosis, and treatment. Using a dataset of intraoperative radiotherapy (IORT) for breast cancer, we analyzed 21 breast tissue samples from patients who received IORT and 16 samples from those who did not. Principal component analysis was employed to reveal data structure, and differentially expressed genes (DEGs) were identified. We constructed a gene network using weighted gene co-expression network analysis and conducted functional enrichment analysis and gene set enrichment analysis. Immune infiltration analysis and protein-protein interaction network analysis were performed, resulting in gene expression heatmaps and Comparative Toxicogenomics Database analysis. Finally, regulatory microRNAs (miRNA) for core genes were predicted using miRNA prediction websites. A total of 2774 DEGs were identified. Principal component analysis demonstrated the differentiation between IORT and non-IORT samples. DEGs were enriched in key biological processes, such as T-cell receptor signaling, immunological synapse formation, and apoptosis. Gene set enrichment analysis validated the functional enrichment of DEGs. Weighted gene co-expression network analysis constructed 15 modules and identified hub genes. Protein-protein interaction network analysis revealed 4 core genes (CD2, CD3D, CD3G, and CD3E). miRNA prediction identified regulatory miRNAs for these core genes. Comparative Toxicogenomics Database analysis revealed that these core genes are associated with breast tumors and inflammation. Immune infiltration analysis showed a high proportion of Macrophages M0 and Macrophages M2 in the samples and revealed correlations between T cells and neutrophils. These findings suggest that the core genes may play key roles in the pathological changes and immune regulation of breast cancer tissues. CD2 and CD3D may serve as potential immune-related biomarkers for IORT in the treatment of breast cancer, influencing tissue pathological changes in breast cancer patients by regulating immune responses and cell signaling pathways.
Chronic fatigue syndrome (CFS) is a debilitating disorder characterized by persistent fatigue with an unclear pathophysiology. Increasing evidence suggests that neuroinflammation plays an important role in the development of CFS; however, the underlying mechanisms remain poorly defined. In this study, we evaluated the effects of edible bird's nest (EBN) in a sleep-deprivation-induced CFS-like mouse model. EBN treatment improved motor and cognitive performance, reduced neuronal necrosis, and preserved synaptic structure in the prefrontal cortex. Blood metabolomic profiling revealed elevated levels of the dipeptide valyl-tryptophan (Val-Trp) following EBN administration. Functional assays showed that Val-Trp attenuates neuroinflammation by suppressing nuclear factor kappa-B signaling, thereby shifting microglia from a pro-inflammatory to a homeostatic state. These findings implicate Val-Trp as a candidate bioactive metabolite associated with the neuroprotective effects of EBN, providing preclinical evidence to support exploration of natural-product-derived interventions for CFS.
The immunosuppressive tumor microenvironment (TME) is a major issue in the malignant progression of glioma patients. The membrane spanning four domains A4A (MS4A4A) has a relationship with M2 polarization of macrophages, and participates in the malignant progression of various cancers. Therefore, exploration of the key role of MS4A4A contributing to glioma biological processes is urgently needed. We performed the bioinformatics analysis of M2 gene expression and built a model predicting the prognosis of glioma patients. Knocking down or overexpressing MS4A4A was achieved in macrophages, and we identified the polarization of macrophages with different MS4A4A expression levels. In vitro and in vivo experiments were used to investigate the role of MS4A4A in regulating M2 polarization and contributing to malignant behaviour in glioma. We found that MS4A4A was associated with the macrophages' M2 scores and the prognosis of GBM patients. MS4A4A had a higher expression level in M2 polarization macrophages. MS4A4A regulates macrophage M2 polarisation through NF-κB and JAK-STAT6 signalling pathways. Macrophages with MS4A4A overexpression promoted the proliferation, invasion, and TMZ-resistance of glioma cells in vitro and in vivo experiments. The treatment targeting the MS4A4A/ NF-κB/STAT6 axis could improve the prognosis and TMZ-resistance in the glioma mouse model. The present study revealed the novel mechanism of the MS4A4A regulating macrophages M2 polarization, contributing to the formation of immunosuppressive tumor microenvironment in glioma through NF-κB/STAT6 signaling pathways, which promotes the malignant biological process of glioma cells. Our results provided new evidence that NF-κB and STAT6 inhibitors might be a potential adjuvant agent in overcoming MS4A4A-mediated chemotherapy resistance in glioma.
The rational design of high-performance microbial cell factories remains a central challenge in sustainable biomanufacturing due to the complexity of metabolic networks and the difficulty of predicting synergistic genetic interventions. Despite recent advances in strain design algorithms, predicting combinatorial targets remains computationally prohibitive due to the combinatorial explosion. Here, we present MetaStrain, a unified computational framework that integrates enzyme-constrained models (ecModels) with meta-heuristic algorithms to identify non-intuitive combinatorial gene targets for improving product yields. MetaStrain first performs pre-screening through a modified enforced objective flux scanning algorithm to reduce the dimensionality of candidate genes and annotate editing strategies. The subsequent search module translates combinatorial editing strategies into numerical encodings compatible with diverse meta‑heuristic algorithms. It then simulates mutant phenotypes by directly modulating enzyme bounds within the ecModels, enabling efficient exploration of the combinatorial design space. Integrated redundancy analysis tools further identify single and fixed‑size combinatorial strategies, facilitating direct experimental implementation. Computational simulation in Saccharomyces cerevisiae reveals significant enhancements in 2-phenylethanol and spermidine biosynthesis, while controlling target count and covering experimentally validated targets. Experimental validation in Escherichia coli further confirmed the algorithm's predictive power, achieving up to a 61.25% increase in L‑tryptophan titer of the five-target combination strain. Overall, MetaStrain achieves high computational efficiency, stable convergence, and broad adaptability across diverse metabolic targets. This study provides a powerful tool for metabolic engineering, bridging computational prediction and experimental realization, and highlighting the potential of meta-heuristic optimization in synthetic biology.
The growing demand for sustainable biomanufacturing has increased interest in nonfood, low-cost carbon feedstocks, particularly methanol and mannitol, owing to their availability and high energy density. However, conventional model microorganisms often show limited efficiency and robustness on such substrates, motivating the exploration of alternative chassis. This review highlights Bacillus methanolicus as an emerging biomanufacturing platform capable of efficiently utilizing both methanol and mannitol. Its thermophilic growth, seawater adaptation, and energy-efficient methanol assimilation pathway provide intrinsic advantages for resource-efficient fermentation processes. We summarize current insights into methanol and mannitol metabolism in B. methanolicus, highlighting that regulation of methanol oxidation and formaldehyde detoxification determines efficient co-utilization, as well as recent advances in synthetic biology tools development that enable rational strain engineering. Finally, we discuss challenges in biomanufacturing from methanol and mannitol, and outline future directions toward establishing B. methanolicus as a versatile platform connecting one-carbon and marine-derived substrates to sustainable chemical synthesis.
The modern phase of human exploration highlights the critical need to understand and mitigate the effects of spaceflight on the human body. Since the first lunar missions, prolonged exposure to microgravity and space radiation has been associated with challenges to the musculoskeletal, immune, and cardiovascular systems; however, the nervous system is emerging as a particularly sensitive target. This review highlights Caenorhabditis elegans (C. elegans) as a model for examining spaceflight-induced neuronal changes, due to its conserved molecular pathways and well-understood nervous system. Recent research shows that microgravity causes morphological changes, including dendritic hyperbranching and self-avoidance defects, which disturb receptive field structure and impair sensory integration. Simultaneously, neuronal waste clearance via exopher pathways becomes less effective, leading to proteostatic overload and feedback stress affecting neuronal function. At a neurochemical level, dopamine and acetylcholine signalling are notably disrupted, while serotonergic and GABA systems also show vulnerabilities, collectively impacting locomotion, behavioral flexibility, and stress resilience. By integrating behavioral, pathological, and molecular insights, this review links neuronal branching, waste clearance, and neurotransmitter regulation as a unified axis of functional disturbance. Ongoing research using C. elegans is crucial to uncover mechanistic pathways and develop countermeasures to safeguard astronaut neurological health, resilience, and performance during future long-duration missions.
Cell-surface glycoRNA plays a crucial role in cellular behavior, yet its RNA substrate signatures and membrane transport mechanism remain unclear. Here, we developed GlycoRNA-Lighted In situ Nano-Tracking (GLINT), an approach for the visualization of distinct RNA-specific glycosignatures. GLINT employs a modular, localized concatenated DNA circuit based on a proximity ligation-mediated dual hierarchical hybridization chain reaction (HCR). Metabolically labeled sialic acid probe and RNA-specific probes are combined into a dual-recognition module through proximity ligation. The module subsequently initiates a dual hierarchical HCR cascade, enabling ultrasensitive in situ tracking of U1, U3, U35a, Y5, and U8 glycoRNAs at the single-cell level. Leveraging GLINT technology, glycoRNAs were confirmed to be transported intracellularly via a SNARE protein-mediated secretory extracellular mechanism. Furthermore, the identification of ten subtypes of breast cancer cells was achieved based on the level of distinct RNA-specific glycosignatures on the cell surface. GLINT demonstrates great potential for tracking RNA-specific glycosignatures, offering a powerful tool for in situ cell subtyping and exploration of RNA-related glycosylation processes.
Van der Waals layered ferroelectrics are considered promising candidates for next-generation nanoelectronic devices. Among these materials, two-dimensional (2D) oxyhalides have gained a significant amount of attention due to their excellent dielectric properties and electronic band structure. However, their ferroelectric polarization has been less extensively explored. In this study, we investigate the intrinsic ferroelectric properties of van der Waals bismuth oxyiodide (BiOI), which was synthesized by using mist chemical vapor deposition. Our findings reveal that BiOI exhibits a high Curie temperature of approximately 450 K, along with both in-plane and out-of-plane ferroelectric domain reversal. Additionally, BiOI-based ferroelectric memristors demonstrate a high switching ratio of 104, long-term retention of 104 s, remarkable cycle stability with up to 10 000 cycles, and the ability to store multistate data. This study provides a solid foundation for the further exploration of the ferroelectric properties of bismuth oxyhalides and paves the way for their potential applications in high-performance ferroelectric memory devices.
Prolonged fasting (PF)-induced hypometabolism shows significant potential for supporting human survival during long-term space missions and in extreme extraterrestrial environments. However, developing safe and effective PF protocols remains a critical challenge for practical application. In the present study, 6- to 7-week-old healthy male Sprague-Dawley (SD) rats were used to investigate PF and intermittent PF (IPF) regimens. Body weight (BW), resting energy expenditure (REE), blood glucose, and ketone body concentrations were measured across PF duration. Based on PF results, two IPF regimens were designed: the 6 + 6 IPF model (6-day fasting/6-day refeeding, repeated twice) and the 4 + 6 + 6 IPF model (4-day fasting followed by three cycles of 6-day refeeding/6-day fasting). Survival rates, food intake, BW, REE, blood glucose, ketone bodies, and metabolic transcriptional responses were analyzed across regimens. PF induced severe weight loss and metabolic switch from glucose to ketone body utilization between days 2- 5 of fasting. The 4 + 6 + 6 IPF model demonstrated superior safety compared to the 6 + 6 IPF model. The 4-day adaptive PF phase in the 4 + 6 + 6 IPF model enables rats to successfully restore BW, REE, blood glucose, and ketone body levels to normal during subsequent fasting-refeeding cycles. This recovery was supported by tissue-specific transcriptional and protein changes in genes related to fatty acid oxidation, lipogenesis, gluconeogenesis, and ketogenesis. Our findings provide evidence of a critical metabolic switch during PF and validated a safe and effective IPF model, contributing to the development of a fasting-induced hypometabolism application for extraterrestrial exploration, however IPF still needs in-depth research in addressing aerospace medicine issues.
The systematic exploration of novel bioactive compounds with superior functional properties is critical for driving innovations in agriculture, healthcare, and related fields, thereby becoming essential for advancing sustainable biotechnological solutions. Nonprotein amino acids (NPAAs), functional amino acids not incorporated into proteins, exhibit unique physiological activities and provide distinctive advantages in nutritional enhancement, functional product formulation, and food/feed processing. These attributes challenge the conventional perception of proteins as mere nutritional carriers, positioning NPAAs as promising bioproducts for biosynthesis and functional applications in agriculture, food, and medicine. This review summarizes the classification of the available NPAAs based on their synthetic substrates for the first time and then outlines their diverse functional roles. A comprehensive analysis of recent advances in biosynthetic pathways, engineering strategies, and production level demonstrates their primary research progress in the laboratory phase. The further sustainable biomanufacturing of NPAAs is hampered by several challenges, including poorly elucidated biosynthetic mechanisms, limited robustness and low productivity of microbial strains, and difficulties in scaling up production for industrial applications. Addressing these bottlenecks will require innovative strategies and technologies to facilitate the translation of NPAA production from bench to industry. This review offers valuable insights into the potential of NPAAs in the development of next-generation bioproducts of nutrition, immune regulation, antioxidant defense, and intestinal homeostasis maintenance, suggesting a promising direction for microbial production of high-performance bioactive molecules in agricultural synthetic biomanufacturing.
The fields of stroke and the gut microbiota are closely linked via the "gut-brain axis," and their complex bidirectional interactions have emerged as a significant research focus. This study represents the first systematic bibliometric analysis of this field, aiming to delineate its knowledge structure, evolutionary trajectory, current research hotspots, and emerging frontiers. Data for this study were retrieved from the Web of Science Core Collection, covering the period from January 1, 2000, to August 31, 2025. Following a screening process, a total of 1,236 relevant articles were included in the analysis. Bibliometric and visualization tools, including CiteSpace, VOSviewer, R software, and Microsoft Excel, were employed to systematically analyze the distribution of research disciplines, publication output, contributions by country/region, institutional collaborations, influential authors, core journals, co-cited references, and keyword co-occurrence. Furthermore, to assess the robustness of our findings and explore characteristic differences across databases, we performed a multi-database validation and comparative analysis using data from Scopus and PubMed. The number of annual publications has shown a continuous increase, with a rapid surge in the number of articles published over the past 5 years, achieving an average annual growth rate of 20.6%. China leads the world in terms of the number of publications, while the United States plays a central role in early-stage research and international collaboration. This study demonstrates significant interdisciplinary integration, encompassing multiple disciplines including neuroscience, pharmacology, immunology, and microbiology. Current research hotspots focus on the interaction between gut microbiota dysbiosis and post-stroke neuroinflammation, the therapeutic potential of microbial metabolites (e.g., short-chain fatty acids), the exploration of gut-brain axis mechanisms, and probiotic intervention strategies. Mechanistic research and clinical translation have been identified as the primary drivers for the development of this field. Multi-database validation showed that the annual publication trends, keyword distribution, and rankings of major contributing countries were consistent. Current research hotspots have expanded from basic mechanisms toward clinical translation, underscoring the importance of elucidating common pathophysiological mechanisms and identifying potential therapeutic targets. Future research priorities include refining screening and diagnostic protocols for gut microbial biomarkers, developing effective prevention strategies based on probiotics and other microbiota-targeted interventions, and advancing individualized and targeted therapeutic approaches. By integrating multi-omics data with precision medicine approaches, the field is poised to further accelerate the translation of mechanistic discoveries into clinical practice, ultimately offering novel strategies for the prevention and treatment of stroke.
Alzheimer's disease (AD) pathogenesis is strongly influenced by APOE4, though how cooperative genetic factors modulate this relationship remains unclear. While genomic studies have tentatively linked RBFOX1 to AD susceptibility, its functional synergy with APOE4 has never been experimentally defined. We engineered APOE3 or APOE4 isogenic human cerebral organoids with CRISPR/Cas9-mediated RBFOX1 knockout. Remarkably, RBFOX1 depletion selectively triggered robust microglial generation exclusively in APOE4 organoids. Time-course gene expression revealed that this APOE4-specific effect correlated with prolonged mesodermal priming during early embryoid body differentiation, creating a permissive niche for microglial lineage specification. The emergent microglia exhibited pronounced neurotoxic phenotypes, including pro-inflammatory factor secretion, synaptic architecture remodeling, and lipid droplet accumulation in organoids. These changes coincided with aggravated Tau hyperphosphorylation and electrophysiological abnormalities, collectively mirroring multifaceted AD pathology. Our findings establish RBFOX1 as a potential AD protective factor, a critical suppressor of APOE4-glia crosstalk, and demonstrate that its loss unleashes a microglia-mediated neurodegenerative cascade. By developing cerebral organoids with autonomous microglial networks, we present a platform capable of modeling genotype-dependent neuron-glia interactions in AD, opening new avenues for mechanistic and therapeutic exploration.
The academic research course of pseudomyxoma peritonei (PMP) has been tortuous and long. It is not until the past 40 years that a cognitive system consistent with the core theories of oncology has gradually been formed, and the level of clinical diagnosis and treatment has also made considerable progress. A comprehensive treatment technology system centered on cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has been established. This article sorts out and summarizes the cutting-edge research progress in the field of PMP at the 15th International Peritoneal Cancer Congress, combines clinical practice to explore its enlightenment for clinical work, scientific research exploration, and the construction of peritoneal oncology discipline in China, aiming to provide reference for the standardized diagnosis and treatment of PMP and related research in China. 腹膜假黏液瘤（PMP）的学术研究历程曲折漫长，直至近40年才逐渐形成符合肿瘤学核心理论的认知体系，随之临床诊疗水平亦取得了长足进步，并构建起以肿瘤细胞减灭术（CRS）加腹腔热灌注化疗（HIPEC）为核心的综合治疗技术体系。本文梳理总结第15届国际腹膜癌大会上PMP领域的前沿研究进展，并结合临床实践，探讨其对临床工作、科研探索及我国腹膜肿瘤学科建设的启示，旨在为我国PMP规范化诊疗和研究提供参考与指导。.
Mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) gastric cancer represents a distinct molecular subtype of gastric cancer. Although immunotherapy has significantly improved survival outcomes in patients with this subtype, its overall efficacy remains limited by primary and acquired resistance. This review provides a comprehensive overview of recent research progress in dMMR/MSI-H gastric cancer,aiming to provide a reference for individualized and precision therapy. (1) It elucidates the molecular definition of dMMR/MSI-H and summarizes the principles, advantages, clinical applications, and limitations of current detection methodologies. (2) It outlines the clinicopathological and molecular biological characteristics of this subtype, emphasizing its unique immunological features. (3) The review examines the evolution and optimization of therapeutic strategies-from conventional chemotherapy to immune checkpoint inhibitor monotherapy and combination immunotherapy-supported by relevant clinical evidence. (4) It further summarizes the underlying mechanisms of immunotherapy resistance, integrates recent studies and emerging strategies to overcome resistance, discusses the ongoing exploration and prospects of organ-preserving treatment strategies, and outlines future research directions. 错配修复缺陷或微卫星高度不稳定（dMMR/MSI-H）型胃癌是胃癌的重要分子亚型，免疫治疗的应用显著改善了该型患者的生存结局，但原发性及继发性耐药仍限制了免疫治疗效果的进一步提升。本文系统综述了dMMR/MSI-H型胃癌的研究进展，希望为患者的个体化精准治疗提供参考。（1）阐述了dMMR/MSI-H的定义，并总结其检测方法的原理、优势、临床应用及挑战；（2）概述dMMR/MSI-H型胃癌的临床病理学和分子生物学特征；（3）重点评述dMMR/MSI-H型胃癌的治疗策略从传统化疗到免疫单药及免疫联合治疗的演变优化及相关循证依据；（4）系统探讨了免疫耐药的潜在机制，归纳克服耐药的应对策略及研究进展，介绍器官保留策略相关的探索与前景，并展望未来研究方向。.