As a core functional component of the tumor microenvironment, the regulatory role of intratumoral microbiome in tumorigenesis and progression has become as a frontier research direction in oncology. Microorganisms such as bacteria, fungi, and viruses participate in the regulation of tumor biological mechanisms through multiple pathways, including metabolite secretion, induction of genomic instability, and remodeling of the immune microenvironment; their species composition and abundance characteristics exhibit distinct cancer-type specificity, and their impact on patient prognosis is highly context-dependent. Current detection systems for the intratumoral microbiome mainly encompass in situ detection technologies, metagenomic sequencing, and computational pathology-driven intelligent detection, each with its own advantages and limitations, among which intelligent detection centered on deep learning is gradually overcoming the technical bottlenecks of identifying low-abundance microbial signals, achieving accurate quantification, and resolving spatial distribution. In the future, with the deep integration of three-dimensional pathological imaging, spatial omics, and multi-modal foundation models, intratumoral microbiome research will advance toward the in-depth development of multi-dimensional data integration, providing innovative ideas and technical pathways for elucidating the regulatory mechanisms between microorganisms and the host and for developing precision diagnostic and treatment strategies based on individual microecological characteristics.

Stereotactic body radiation therapy (SBRT)/stereotactic ablative radiation therapy (SABR), leveraging its precision and high efficiency, has become an important radical treatment modality for early-stage non-small cell lung cancer, particularly suitable for patients who are inoperable or refuse surgery. With advances in radiotherapy technology and in-depth clinical research, its clinical applications have been continuously expanding. To standardize clinical practice, improve treatment homogenization, and facilitate collaborative research, the expert panel developed this consensus based on domestic and international evidence and practical experience. This consensus covers five core components: (1) reviewing the developmental history and key research outcomes of SBRT/SABR; (2) defining standards for equipment configuration, treatment planning, and quality assurance; (3) refining patient selection, treatment workflow, and efficacy evaluation; (4) discussing strategies and safety management of SBRT/SABR combined with immunotherapy/targeted therapy; (5) providing recommendations for managing complex scenarios such as central lung cancer. This consensus aims to provide clinicians with standardized guidance, optimize treatment decisions, enhance patient benefits, and promote the high-quality development of SBRT/SABR in China, ultimately benefiting a broader population of patients with lung cancer.

Low-dose radiotherapy (LDRT), as an emerging tumor immunomodulatory strategy, has demonstrated its synergistic anti-tumor potential when combined with immunotherapy in multiple solid tumors. Unlike traditional high-dose radiotherapy that directly kill tumors, LDRT reshapes the tumor immune microenvironment by promoting dendritic cell antigen presentation, enhancing T-cell infiltration, reversing the immunosuppressive microenvironment, and remodeling tumor vascular and stromal structures, thereby enhancing the efficacy of immunotherapy. Clinical studies have shown that LDRT combined with immune checkpoint inhibitors, chemotherapy, or high-dose radiotherapy can increase the objective response rate and improve patient survival in solid tumors such as non-small cell lung cancer, extensive-stage small cell lung cancer, and head and neck squamous cell carcinoma, with favorable safety profiles. However, unified standards for LDRT are still lacking in terms of patient selection, combination strategies, dose fractionation, sequencing, and target volume delineation. Based on current basic research and clinical evidence, this expert consensus, titled "Expert consensus on application specifications of low-dose radiotherapy in solid tumors (2026 edition)", systematically elaborates on the mechanisms, clinical applications, and recommended regimens of LDRT, aiming to promote its standardized application and providing a reference for future clinical research and practice.

Fertility preservation in women with recurrent serous borderline ovarian tumors (SBOTs) remains clinically challenging because of concerns regarding oncological safety and limited evidence. We report the case of a young woman with FIGO Stage IIIA1 SBOT with lymph node involvement who experienced multiple recurrences with adverse pathological features, including micropapillary architecture and stromal microinvasion. Following multidisciplinary discussion and comprehensive counseling, a brief micro-stimulation in vitro fertilization protocol was performed for embryo cryopreservation prior to repeat fertility-sparing surgery to minimize treatment delay. After complete macroscopic disease clearance, frozen-thawed embryo transfer was carried out, resulting in a successful term live birth. No clinical or radiological evidence of recurrence was observed during the available follow-up period. This case suggests that an individualized fertility-first strategy may be considered in carefully selected patients with advanced recurrent SBOT under strict multidisciplinary evaluation and close surveillance.

The heparin wet suction technique (HWST) may improve tissue quality in endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) by preventing blood clot formation within the needle. We compared the diagnostic performance and safety of HWST with the conventional suction technique (CST), using a novel 22-gauge FNB needle in patients with solid pancreatic masses.

In this multicenter, single-blinded, randomized crossover trial, patients with solid pancreatic masses (≥ 1 cm) were randomized 1:1 to HWST-first or CST-first. Each patient underwent one pass with each technique using the novel 22-gauge needle. The primary outcome was diagnostic yield; secondary outcomes included technical success, adverse events, and adequacy for immunohistochemistry (IHC).

Of 174 randomized patients, 170 received both interventions and were analyzed; baseline characteristics were comparable. The diagnostic yield was 82.9% (95% confidence interval [CI], 76.6-87.9) with HWST and 83.5% (95% CI, 77.2-88.4) with CST. The paired difference was -0.6 percentage points (95% CI, -6.7 to 5.5; exact McNemar p = 1.000). The combined diagnostic yield after sequential sampling was 91.2% (95% CI, 86.0-94.6). Technical success was 100% with both techniques, and IHC adequacy was similar (HWST: 80.6% vs. CST: 78.8%). One self-limiting bleeding event occurred during CST.

HWST showed diagnostic yield, technical success, and safety comparable to CST. Both techniques are highly effective for EUS-FNB of solid pancreatic masses. Sequential sampling may improve overall diagnostic yield, although this finding should be interpreted cautiously and requires further validation.

CD4⁺CD25⁺FOXP3⁺ regulatory T cells (Treg) are highly activated in tumors and promote disease progression. Specific, universal targeting of these effector Treg cells is limited by the lack of a conserved signature across human cancers and information on their origin. Here we combine analysis of single-cell RNA-sequencing datasets with spectral flow cytometry and identify a core signature of 88 genes consistently upregulated in intratumoral Treg cells among 9 epithelial cancers. We describe 4 Treg cell subsets - CCR7⁺ quiescent, CCR8⁺ effector, CD161⁺ and intermediate, with distinct tissue distribution, function, differentiation trajectories and molecular drivers. By single-cell T cell receptor sequencing, we observe that protumoral, effector CCR8⁺ Treg cells exhibit little clonal relationship with other Treg cell subsets inside tumors, but are clonally related to Treg cells in tumor-draining lymph nodes, as well as conventional T cells in tumors. This resource provides insights for development and fine-tuning of CCR8⁺ Treg cell-targeting therapies in cancer.

The Regulator of Cullins 1 (ROC1) or RING box protein-1 (RBX1) is an essential component of the largest multiunit Cullin-RING ubiquitin ligase (CRL). Previous studies demonstrated that ROC1 is frequently overexpressed in multiple malignancies, which predicts advanced cancer stages and poor prognosis. However, the molecular mechanisms driving ROC1 overexpression in cancers remain largely unknown. Herein, we reveal that HSP90 binds to ROC1 with its N-Terminus, thus promoting ROC1 stabilization. HSP90 inhibition with the N-Terminal, but not the C-Terminal inhibitors accelerate ROC1 destabilization by facilitating its ubiquitination and subsequent degradation by CHIP E3 ligase. CHIP specifically interacts with ROC1 at its CC domain, thus promoting the K48-linked-ubiquitin-mediated degradation of ROC1 at the K26 residue. Indeed, deletion of CHIP markedly blocks HSP90-inactivation-induced ROC1 reduction. Function exploration reveals that HSP90 inhibition suppresses lung adenocarcinoma (LUAD) cell growth substantially by decreasing ROC1 abundance. In clinic, HSP90β and ROC1 are overexpressed in LUAD samples, which have positive correlation and predict poor prognosis of LUAD patients. LUAD organoids analysis reveals that HSP90 blockage promotes ROC1 destabilization and inhibits the growth of organoid cells. Taken together, the present results demonstrate the regulatory mechanism of ROC1 in malignancies and suggest a novel mechanism of the oncogenic role of HSP90 to promote lung tumorigenesis.

The primary aim was to conduct a longitudinal pharmacoepidemiological study on the dispensing patterns of the influenza and pneumococcal vaccines in a section of the private healthcare sector in South Africa in the presence of the COVID-19 vaccine to document the dispensing of these two respiratory vaccines alongside COVID-19 vaccines.

A quantitative cross-sectional pharmacoepidemiological study on health insurance data covering 5 years (2017-2021) was conducted. The study population consisted of approximately 3.8 million individuals. Profile analysis was used to compare annual dispensing patterns of both vaccines. Ethical approval for the study was obtained.

The annual dispensing patterns of the pneumococcal and influenza vaccines differed significantly for the period 2017-2021 (p-value < 0.01), with the influenza vaccine dispensed most frequently from March to June. A similar pattern was observed for both the pre-COVID-19 period (2017-2019) (p-value < 0.01) and the post-COVID-19 period (2020-2021) (p-value < 0.01). At the 5% level of significance, there was a slight increase in the dispensing pattern of pneumococcal vaccines post-COVID-19, when compared to the dispensing pattern pre-COVID-19 (p-value < 0.05). For the period March to June, there was, however, a significant increase in the dispensing pattern of influenza vaccines post-COVID-19 (p-value < 0.01).

The presence of the COVID-19 vaccine has collectively not had a significant impact on the dispensing patterns of pneumococcal and influenza vaccines. When considering the vaccines separately, however, for the months between March and June, significantly more influenza vaccines were dispensed post-COVID-19.

Pediatric sepsis, a major cause of acute lung injury (ALI), involves a dysregulated host response. Cuproptosis is a novel copper-dependent cell death process regulated by Ferredoxin 1 (FDX1). However, its role in pediatric sepsis-associated ALI is unknown. This study investigated the upstream regulation mechanism of FDX1, and its role in pediatric sepsis-related ALI.

Peripheral blood mononuclear cells (PBMCs) were collected from septic children and healthy controls. All enrolled pediatric subjects were divided into three groups: healthy control group (N = 40), sepsis without ALI group (N = 30), and sepsis with ALI group (N = 30). The clinical significance of FDX1, steroidogenic factor 1 (SF1), and Jun proto-oncogene (cJUN) was assessed by qRT-PCR. A septic ALI cell model was established using LPS-treated BEAS-2B cells. Functional assays (CCK-8, TUNEL, ELISA) assessed viability, apoptosis, and inflammation. An in vivo cecal ligation and puncture (CLP) model was employed to confirm the role of FDX1. Molecular mechanisms (transcriptional regulation, protein interaction) were examined via ChIP, dual-luciferase, and Co-IP.

FDX1, SF1, and cJUN levels were significantly elevated in pediatric sepsis patients, especially in those complicated with ALI, and the three genes were positively correlated with each other. In vitro, LPS induced BEAS-2B cell injury, inflammation, and cuproptosis. FDX1 overexpression exacerbated these effects, while its knockdown exerted protective effects. Mechanistically, SF1 directly bound to the FDX1 promoter to activate its transcription. SF1 physically interacted with cJUN, and they synergistically enhanced FDX1 transcription. Knockdown of cJUN abolished SF1-mediated FDX1 upregulation and its pro-cuproptotic effects. In vivo experiments demonstrated that FDX1 knockdown attenuated CLP-induced lung injury, inflammation, and cuproptosis.

SF1, cJUN, and FDX1 may be closely involved in pediatric sepsis-related ALI. The physical interaction between SF1 and cJUN potentially modulates FDX1 transcription, which may contribute to cuproptosis and pediatric sepsis-related ALI progression.

Ketone body levels are elevated in patients with heart failure (HF). Recently, plasma levels of ketone bodies have been associated with mortality in patients with HF. However, little is known about the biological processes active in patients with high levels of ketone bodies. The objective of this study was to investigate the features and prognosis of patients with HF with elevated β-hydroxybutyrate levels. Furthermore, we aimed to determine the specific biological processes that are active in these patients that may result in elevated levels of β-hydroxybutyrate.

β-hydroxybutyrate concentrations were measured by nuclear magnetic resonance spectroscopy in plasma from 478 patients with HF from the BIOSTAT-CHF cohort. In addition, the concentrations of 1057 circulating proteins were measured by liquid chromatography-mass spectrometry. Differential expression and ingenuity pathway analyses were used to investigate which biological processes are associated with high levels of β-hydroxybutyrate. Cox regression was used to investigate the association of β-hydroxybutyrate with mortality and HF hospitalization. Mediation analysis was conducted to determine how much of the association between β-hydroxybutyrate and outcomes is statistically explained by these processes.

The cohort consisted mostly of male patients (64.2%), with equal proportions of HF with reduced ejection fraction and preserved ejection fraction. Elevated β-hydroxybutyrate levels were independently associated with higher heart rate, lower iron levels, and lower body mass index. Moreover, every doubling of β-hydroxybutyrate was associated with a 36.4% increase in mortality (unadjusted hazard ratio 1.364: 95% confidence interval 1.089-1.707). Even after accounting for known risk factors, the relationship remained highly robust (adjusted hazard ratio 1.389; 95% confidence interval 1.150-1.677). Differential expression and ingenuity pathway analyses revealed that higher β-hydroxybutyrate levels were associated with the upregulation of pathways associated with acute inflammation and cachexia, whereas lipogenic and anabolic pathways were down-regulated. Subsequent multiple mediation analysis showed that 76% of the association between β-hydroxybutyrate and mortality was explained by these pathways.

Elevated β-hydroxybutyrate levels predict mortality in chronic HF, independent of established risk factors. Proteomic analysis links elevated β-hydroxybutyrate to heightened inflammation and catabolism, and these pathways largely mediated the association between β-hydroxybutyrate and mortality. These findings suggest that elevated ketone bodies may reflect underlying metabolic stress in patients at risk of adverse outcome.