Baolin Qu

Background: Longitudinal changes in the fecal microbiome and metabolome during concurrent chemoradiotherapy (CCRT) for rectal cancer remain incompletely characterized. Methods: In this prospective single-center cohort, 19 patients with rectal cancer were enrolled and 17 were included in the longitudinal analysis after two prespecified sampling-window exclusions. Fecal specimens were scheduled at nine time points: R0, collected before the first dose of capecitabine and before radiotherapy, and R3 through R24 at three-fraction intervals during treatment. Twenty unmatched healthy volunteers provided one fecal specimen for a descriptive pretreatment comparison. Full-length 16S rRNA gene sequencing and untargeted metabolomics were performed. Longitudinal microbial counts were analyzed using negative-binomial generalized linear mixed models, and metabolite features were analyzed using linear mixed-effects models; participant was included as a random intercept, and P values were adjusted using the Benjamini–Hochberg false discovery rate (FDR). Results: Nineteen genera and 27 of 176 analyzed species showed significant linear time trends during CCRT (FDR < 0.05). Parvimonas micra, Peptostreptococcus stomatis , and Gemella morbillorum decreased, whereas Lachnoclostridium pacaense, Blautia hydrogenotrophica, [Eubacterium] sulci , and Coprococcus eutactus increased. Of 2,873 analyzed metabolic features, 393 changed significantly over time. In a secondary same-cohort analysis, 17 of 50 correlation-selected taxon-metabolite pairs remained significant in time-adjusted mixed-effects models, including a positive association between C. eutactus and a feature annotated as stercobilin. Among 103 significant features with KEGG identifiers, three pathways met a nominal raw-P threshold, but none remained significant after FDR correction. Pretreatment patient samples had lower Shannon diversity and differed from healthy-control samples by ANOSIM; these comparisons were descriptive because the groups were not matched for age or sex. Five species shared the same case-control direction in this cohort and GMrepo reports, but only P. stomatis and G. morbillorum also showed significant longitudinal declines during CCRT. Conclusion: This small, intensively sampled cohort identifies exploratory fecal microbial and metabolic trajectories during capecitabine-based CCRT. The findings do not establish causal mechanisms, microbial functions, disease specificity, or biomarker performance and require independent confirmation in larger cohorts.

Accurate vessel segmentation in X-ray angiography (XRA) is essential for diagnosing coronary artery disease and supporting interventional procedures. However, low contrast, complex backgrounds, and substantial variation in vessel caliber make accurate segmentation challenging, especially for thin vessels. We propose a Vascular-Aware Mixture-of-Experts (VA-MoE) framework for XRA vessel segmentation. The model incorporates Dynamic Snake Convolution (DSnC) to capture the elongated and curved morphology of vessels and a Texture-Enhanced Decoder (TED) to recover fine spatial details and suppress background noise during upsampling. The proposed framework was evaluated on three representative datasets: ARCADE, DCA1, and XCAD. VA-MoE achieved an IoU of 87.80% and a Dice coefficient of 93.08% on ARCADE, an IoU of 65.18% and a Dice coefficient of 78.03% on DCA1, and an IoU of 67.52% and a Dice coefficient of 79.93% on XCAD. Compared with the strongest baseline methods, VA-MoE improved IoU and Dice by 2.77 and 1.21 percentage points on ARCADE, by 2.40 and 2.10 percentage points on DCA1, and by 2.89 and 1.50 percentage points on XCAD, respectively. Qualitative results further suggested improved topological continuity and better preservation of thin peripheral vessels compared with competing methods. The proposed VA-MoE framework provides a promising solution for XRA vessel segmentation. By jointly enhancing vascular structural modeling and texture recovery, it may support automated cardiovascular image analysis.

Extensive-stage small cell lung cancer (ES-SCLC) is an aggressive malignancy with an extremely poor prognosis. For a long time, platinum-based chemotherapy combined with etoposide has been the primary treatment option. Although the initial response rate is high, the vast majority of patients face the dilemma of rapid recurrence and drug resistance. In recent years, the application of immunotherapy has brought about a significant breakthrough in the treatment of ES-SCLC. Multiple Phase III clinical trials have demonstrated that combining immune checkpoint inhibitors with traditional chemotherapy regimens as first-line treatment significantly improves the median overall survival (OS) and progression-free survival (PFS) in patients, while maintaining manageable safety profiles. Therefore, chemotherapy combined with immunotherapy has become the new standard for first-line treatment of ES-SCLC worldwide. However, the absolute survival benefit from immunotherapy remains limited. Against this backdrop, thoracic radiotherapy (TRT), as an effective local treatment modality, shows potential for further survival gains. The combination of chemoimmunotherapy and TRT is emerging as a key area of current clinical exploration. However, the characteristics of the patient population that may benefit most from this treatment modality, as well as the optimal dose and timing of TRT, remain under investigation. Furthermore, the predictive value of previously discussed biomarkers in this combination therapy strategy for ES-SCLC remains unclear. Therefore, this paper reviewed recent advances in treatment strategies and candidate biomarkers for ES-SCLC, with a particular focus on the evolving role of thoracic radiotherapy in the era of immunotherapy.

This study compared deep inspiration breath-hold (DIBH) versus free-breathing (FB) techniques in postoperative radiotherapy for left-sided breast cancer. Dosimetric parameters for 94 patients were analyzed. DIBH significantly improved target conformity while reducing cardiac exposure, with mean heart dose decreasing by 2.631 Gy (EQD2). Significant dose reductions were also observed in bilateral lungs, esophagus, and spinal cord. A weak correlation was identified between left lung volume expansion and organ-at-risk dose reduction. Receiver operating characteristic analysis determined that a left lung volume increase of 807.1 cc predicted clinically meaningful cardiac protection. DIBH demonstrates effective organ sparing while only marginally compromising target coverage. Additionally, lung volume expansion could serve as a potential patient selection criterion.

Ultra-high dose rate (FLASH) radiotherapy is a novel modality delivering dose rates several orders of magnitude higher than conventional dose rate (CONV) radiotherapy. FLASH radiotherapy has been shown to significantly reduce the damaging effects on normal tissues while achieving similar tumor control, a phenomenon referred to as the FLASH effect. Radiation-induced lung injury (RILI) represents a prevalent complication in thoracic tumor radiotherapy, significantly compromising treatment outcomes and patient quality of life. Emerging preclinical evidence consistently demonstrates that FLASH radiotherapy significantly attenuates radiation-induced lung injury compared to CONV radiotherapy. The observed radioprotection primarily manifests in structural preservation of alveolar epithelium, pulmonary vasculature, and bronchial networks, concomitant with substantial reductions in both radiation pneumonitis and subsequent pulmonary fibrosis. Current evidence suggests that RILI pathogenesis involves multiple mechanisms, including DNA damage and repair, reactive oxygen species (ROS) and oxidative stress, inflammation, and immune response. These mechanistic insights provide a crucial foundation for investigating the radiobiological basis of the FLASH effect. Our review summarizes the preclinical studies of FLASH radiotherapy in mitigating lung injury. Furthermore, it explores the potential mechanisms underlying the FLASH effect from the perspective of the biological mechanism of RILI, aiming to provide a reference and direction for the clinical translation of FLASH radiotherapy.

Radiotherapy is a major source of ionizing radiation that adversely affects the male reproductive system. FLASH radiotherapy (FLASH-RT), a novel technique delivering ultra-high dose rate (UHDR) radiation, has shown promise in reducing normal tissue damage while maintaining antitumor efficacy—a phenomenon known as the “FLASH effect”. Male fertility depends on the coordinated function of spermatogenic, Sertoli, and Leydig cells in the testes, which display differential sensitivity to radiation exposure. Due to ethical limitations in human studies, rodent models are indispensable for exploring radiation-induced testicular injury. This review summarizes current evidence of the FLASH effect across rodent organs and the impact of ionizing radiation at different dose rates on testicular cells. Given the current lack of direct evidence for the FLASH effect in testicular tissue, it also reviews mechanisms observed in other organs that may contribute to its potential protective role in the testes. A deeper understanding of these mechanisms could inform fertility-preserving strategies in male cancer patients receiving radiotherapy.

Background: Immune checkpoint inhibitors (ICIs) as part of first-line treatment are becoming increasingly significant in metastatic non-small cell lung cancer (NSCLC). We aimed to investigate the efficacy and safety of thoracic radiotherapy (TRT) in addition to first-line ICIs in metastatic NSCLC. Methods: From January 2017 to August 2023, we retrospectively collected the information of 82 patients with metastatic NSCLC who were treated with first-line ICIs and radiotherapy (RT). Patients were divided into the TRT group (n=35) and the non-TRT group (n=47). The efficacy and safety were analyzed. Propensity score matching (PSM) was applied. Inverse probability of treatment weighting (IPTW) was used as a sensitivity analysis. Results: The median follow-up was 31.4 months (range, 4.0–81.4 months). Before PSM, the median overall survival (OS; 38.1 vs. 17.9 months, P=0.01) and median progression-free survival (PFS; 14.9 vs. 8.3 months, P=0.001) were significantly improved in the TRT group. After PSM, there were 18 patients in each group. Both the median OS [not reached (NR) vs. 26.8 months, P=0.02] and median PFS (16.3 vs. 7.5 months, P0.99) or after matching (0 vs. 5.6%, P>0.99). Conclusions: The addition of TRT to first-line immunotherapy (IO) may be associated with improved survival in metastatic NSCLC. However, given the retrospective nature and limited sample size, these findings are exploratory and warrant validation in larger randomized trials.

Background and purpose Radiation-induced lung injury (RILI) limits the efficacy of thoracic radiotherapy. However, the underlying mechanism of RILI remains unclear. cGAS-STING pathway is reported to be involved in the recognization of cytosolic dsDNA and various inflammatory diseases. This study aimed to investigate the role of cGAS-STING pathway in the development of RILI. Materials and methods A pre-clinical mouse model of RILI was established by whole thorax irradiation and confirmed using H&E and Masson’s trichrome staining. STING agonist (DMXAA) and antagonist(C-176) were administrated to modulate cGAS-STING pathway in vivo. Western blot and ELISA were used to determine the expression levels of different proteins. Results Quantitation analysis showed dsDNA accumulation in lung tissue and western blot showed the up-regulation of cGAS and STING protein level post-irradiation, indicating pathway activation. Histological evaluation showed that C-176 administration ameliorated radiation-induced pulmonary inflammation and fibrosis, while DMXAA exhibited contrary effects. In further in vitro study, the release of dsDNA induced by radiation led to the activation of cGAS-STING pathway in RAW 264.7 cells, resulting in the polarization into M1 phenotype and pro-inflammatory production. Conclusion In summary, our data demonstrated a link between cGAS-STING pathway and the development of RILI, indicating its potential application in clinic.