G protein-coupled receptors (GPCRs) are the largest family of membrane proteins and play a critical role as pharmacological targets. An improved understanding of GPCRs’ involvement in tumor microenvironment may provide new perspectives for cancer therapy. This study used machine learning to classify head and neck squamous cell carcinoma (HNSCC) patients into two GPCR-based subtypes. Notably, these subtypes showed significant differences in prognosis, gene expression, and immune microenvironment, particularly CD8⁺ T cell infiltration. S1PR4 emerged as a key regulator distinguishing the subtypes, positively correlated with CD8⁺ T cell proportion and cytotoxicity in HNSCC. It was predominantly expressed in CX3CR1⁺CD8⁺ T cells among T cells. Upregulation of S1PR4 enhanced T cell function during CAR-T cell therapy, suggesting its potential in cancer immunotherapy. These findings highlight S1PR4 as an immune modulator for favorable prognosis in HNSCC, and offer a potential GPCR-targeted therapeutic option for HNSCC treatment.

Background: Self-expanding metal stents (SEMS) served as a bridge to surgery (BTS). However, this method may be associated with worse long-term prognosis and relapse of CRC patients. Therefore, we attempted to clarify this in the angle of circulating tumor cells (CTCs). Methods: A multicenter study was performed from March 2018 to January 2021. Thirty-two colorectal cancer patients with obstruction were selected, of which 21 patients were performed SEMS as a BTS while 11 patients were performed emergency surgery. Bloods samples were collected in two groups of patients for further detecting CTCs. In the SEMS group, the samples were collected before and after stent insert and after radical surgery performed. In the ES group, the samples were collected before stent insert and after emergency surgery performed. Results: The number of CTCs did not show statistically significant differences before and after stent placement (34.90 vs 38.33, p=0.90), neither between the SEMS group and ES group in initial CTC levels (34.90 vs 58.09, p=0.394). No significant differences (38.33 vs 58.09, p=0.632) were observed after stent insert in the SMES group and the initial CTC levels in the ES group. Moreover, no major differences (24.17 vs 42.27, p=0.225) were observed after radical operation performed in both groups. Conclusion: The treatment of SEMS does not cause an increase in the number of CTC after stent insertion. Furthermore, there are may be other factors besides CTC to cause these poorer oncologic outcomes after SEMS placement.

Background: Currently, a comprehensive method for exploration of transcriptional regulation has not been well established. We explored a novel pipeline to analyze transcriptional regulation using co-analysis of RNA sequencing (RNA-seq), assay for transposase-accessible chromatin using sequencing (ATAC-seq), and chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq).Methods: The G protein-coupled receptors (GPCRs) possibly associated with macrophages were further filtered using a reduced-Cox regression model. ATAC-seq profiles were used to map the chromatin accessibility of the GPRC5B promoter region. Pearson analysis was performed to identify the transcription factor (TF) whose expression was correlated with open chromatin regions of GPRC5B promoter. ChIP-seq profiles were obtained to confirm the physical binding of GATA4 and its predicted binding regions. For verification, quantitative polymerase chain reaction (qPCR) and multidimensional database validations were performed.Results: The reduced-Cox regression model revealed the prognostic value of GPRC5B. A novel pipeline for TF exploration was proposed. With our novel pipeline, we first identified chr16:19884686-19885185 as a reproducible open chromatin region in the GPRC5B promoter. Thereafter, we confirmed the correlation between GATA4 expression and the accessibility of this region, confirmed its physical binding, and proved in vitro how its overexpression could regulate GPRC5B. GPRC5B was significantly downregulated in colon adenocarcinoma (COAD) as seen in 28 patient samples. The correlation between GPRC5B and macrophages in COAD was validated using multiple databases.Conclusion: GPRC5B, correlated with macrophages, was a key GPCR affecting COAD prognosis. Further, with our novel pipeline, TF GATA4 was identified as a direct upstream of GPRC5B. This study proposed a novel pipeline for TF exploration and provided a theoretical basis for COAD therapy.

Weakly supervised segmentation of cancerous regions in whole-slide images (WSIs) is a crucial task in computational pathology, but it is severely hampered by the need for expensive pixel-level annotations. Existing Multiple Instance Learning (MIL) frameworks, while popular, typically fail to produce accurate segmentation masks because they treat WSIs as an unordered ’bag-of-patches’, ignoring the critical tissue topology and architectural patterns that define malignancy. In this paper, we address this fundamental limitation by proposing Geometric Multi-Instance Learning (Geo-MIL), a novel graph-based framework that explicitly models the spatial relationships between tissue patches. At the core of our method is a new topological attention mechanism that operates on the WSI graph, learning to identify and prioritize entire diagnostically relevant tissue structures over isolated patch features. Through extensive experiments on three public gastric cancer datasets, we demonstrate that Geo-MIL significantly outperforms a wide array of state-of-the-art baselines, achieving a new benchmark in both segmentation accuracy and classification performance. Our work represents a significant step towards bridging the gap between weak slide-level labels and precise, pixel-level predictions, paving the way for scalable and accurate quantitative analysis in digital pathology.

Sclerosing encapsulating peritonitis (SEP) is a rare cause of intestinal obstruction that is characterized by a thick greyish-white fibrotic membrane encasing the small bowel. The clinical features are typically nonspecific, and they occasionally present with recurrent episodes of incomplete or complete intestinal obstruction. The etiology of SEP remains unclear, and the diagnosis is often delayed mainly due to the lack of specific symptoms. Here, we first report a patient who suffered from SEP after treatment for malignant mesothelioma (MM) with tumor resection supplemented with hyperthermic intraperitoneal chemotherapy (HIPEC) once and intraperitoneal chemotherapy (IPC) eight times. The patient was discharged ten days after surgery and was free of complications at the 4-month follow-up. In addition, we reviewed the published literature from PubMed, only 7 articles of 16 cases finally met the defined requirements. Nine cases of SEP after IPC and 7 cases of SEP after HIPEC were previously reported. We synthetically review the pathogenesis, treatments, and outcomes. In conclusion, SEP is a rare abdominal disease, which is difficult to diagnose preoperatively. CT scanning is the most helpful imaging method for the diagnosis of SEP. Surgery is the most effective method for diagnosis and treatment, if conservative treatment has no effect or abdominal symptoms are aggravated.