Wu Song

Introduction: The role of prophylactic ileostomy (PI) and its potential to reduce the risk of postoperative complications such as anastomotic leakage remains unclear. Methods: The PILLAR study (2018–2020, China, 17 centers) prospectively compared PI versus nonprophylactic ileostomy (NPI) in patients undergoing laparoscopic low anterior resection for rectal cancer. The primary endpoint was the anastomotic leakage rate. Secondary endpoints included postoperative complications, leakage management/outcomes, and leakage-associated risk factors. Results: A prospective study was conducted to gather data from 728 patients who underwent laparoscopic low anterior resection for rectal cancer, 192 (26.4%) of whom underwent PI. Seven cases of anastomotic leakage were observed in the PI group (3.6%) and 25 cases were observed in the NPI group (4.7%). Statistical analysis revealed no significant difference in the incidence of anastomotic leakage between the two groups. Moreover, the total complication rates were 17.2% in the PI group and 10.3% in the NPI group ( P = 0.012). However, the patients with anastomotic leakage in the NPI group had more severe abdominal infections, as evidenced by the C-reactive protein (CRP) values on postoperative day 5 (184.1 ± 72.2 and 77.2 ± 17.0 mg/L in the NPI and PI groups, respectively) ( P < 0.001). Patients’ postoperative procalcitonin (PCT) values similarly support this conclusion. Notably, despite this difference in infection severity, there was no statistically significant difference in the treatment or outcomes of patients with anastomotic leakage in either group. Furthermore, male sex and CRP levels on the fifth postoperative day are identified as independent risk factors for anastomotic leakage. Conclusions: PI may have failed to decrease the incidence of anastomotic leakage in patients who underwent laparoscopic low anterior resection for rectal cancer. Given the higher complication rate associated with PI, its use as a preventive measure for patients at risk of anastomotic leakage should be carefully considered.

Pelvic surgeries frequently injure the pelvic autonomic plexus, represented in rats by the major pelvic ganglia (MPG), resulting in refractory erectile dysfunction (ED) with limited therapeutic options. Sacral neural crest (NC) cells, the embryonic progenitors of MPG neurons and glial cells, offer a developmentally matched cell source for targeted neural repair. We developed a stable and expandable sacral NC cell population derived from human pluripotent stem cells (hPSCs) and transplanted these cells into a rat model of MPG crush injury to assess engraftment efficacy and functional outcomes. Transplantation of sacral NC cells resulted in robust engraftment and significant erectile functional recovery, as evidenced by elevated intracavernosal pressure/mean arterial pressure (ICP/MAP) ratios. Mechanistically, MPG repair involves dual pathways: differentiation into nitrergic and cholinergic neurons and glial cells, which is coupled with the sustained secretion of neurotrophic factors (BDNF/GDNF/NGF). MPG restoration thereby re-established autonomic innervation of the penis, driving structural recovery characterized by reduced apoptosis and fibrosis, as well as the restoration of smooth muscle and endothelial integrity—essential for erectile functional rehabilitation. Our results demonstrate that hPSC-derived sacral NC cells represent a novel therapeutic strategy for neurogenic ED, restoring pelvic autonomic nerve structure and function through both neurogenic differentiation and sustained neurotrophic support.

Ensuring accurate cell type annotation in single-cell RNA sequencing data is a significant challenge, as both expert and automated methods can be biased or constrained by their training data, leading to errors and time-consuming revisions. To address this, we developed LICT (Large Language Model-based Identifier for Cell Types), a tool that leverages multi-model integration and a “talk-to-machine” approach. Validated across diverse datasets, LICT consistently aligns with expert annotations. With its objective framework for assessing annotation reliability, LICT can interpret cases where a single cell population exhibits multifaceted traits, allowing researchers to focus on the underlying biological insights. Comparisons with existing tools highlight LICT’s superiority in efficiency, consistency, accuracy, and reliability, establishing it as a powerful tool for single-cell RNA sequencing analysis. Furthermore, its independence from reference data emphasizes LICT’s generalizability, enhancing reproducibility and ensuring more reliable results in cellular research.

Purpose: The peritoneum is a common site of metastasis in gastric cancer (GC), associated with poor prognosis and significant morbidity. The proclivity of GCs to metastasize to the peritoneum has been hypothesized to occur due the latter’s immunosuppressive microenvironment, such as stromal infiltration and M2 macrophage enrichment, which are associated with increased risk of PM. As far as we know, a model that can effectively predict the prognosis of patients with GCPM is still lacking. Consequently, we constructed a prognostic risk model based on M2 macrophages associated with gastric cancer peritoneal metastasis, aiming to enhance predictive precision and guide tailored therapeutic interventions. Methods: M2 macrophage-associated genes were identified in combination with marker genes from single-cell RNA sequencing (scRNA-seq) and modular genes from weighted gene coexpression network analysis (WGCNA). A prognostic model was constructed via LASSO analysis and validated in internal and external cohorts. We further compared the immune microenvironment, immune checkpoints, and chemotherapeutic drug sensitivity between patient groups stratified by risk to clarify the immune landscape in the GCPM. Results: Our study identified 38 M2 macrophage-related genes via single-cell and bulk RNA sequencing. We developed a prognostic model based on the expression levels of 4 signature genes: DAB2, SPARC, PLTP, and FOLR2. The feasibility of the model was validated with internal and external validation sets (TCGA, GSE62254 and IMvigor210). The model also supported the prediction results of prognosis on the basis of the immunohistochemical results. Notably, patients with higher risk scores had a lower proportion of MSI-H and TMB, a higher prevalence of stages III–IV, and a lower likelihood of responding favorably to immunotherapy. Conclusion: Our prognostic risk model could effectively predict the prognosis and response to chemo-immune therapy in patients with GCPM. The risk score is a promising independent prognostic factor that is closely correlated with the immune microenvironment and clinicopathological characteristics.

The extracellular matrix (ECM) has been demonstrated to be dysregulated and crucial for malignant progression in gastric cancer (GC), but the mechanism is not well understood. Here, that discoidin domain receptor 1 (DDR1), a principal ECM receptor, is recognized as a key driver of GC progression is reported. Mechanistically, DDR1 directly interacts with the PAS domain of hypoxia‐inducible factor‐1α (HIF‐1α), suppresses its ubiquitination and subsequently strengthens its transcriptional regulation of angiogenesis. Additionally, DDR1 upregulation in GC cells promotes actin cytoskeleton reorganization by activating HIF‐1α/ Ras Homolog Family Member A (RhoA)/Rho‐associated protein kinase 1 (ROCK1) signaling, which in turn enhances the metastatic capacity. Pharmacological inhibition of DDR1 suppresses GC progression and angiogenesis in patient‐derived xenograft (PDX) and organoid models. Taken together, this work first indicates the effects of the DDR1‐HIF‐1α axis on GC progression and reveals the related mechanisms, providing experimental evidence for DDR1 as a therapeutic target for GC.

Background: Circular RNAs (circRNAs) have been proved to play crucial roles in the development of various cancers. However, the molecular mechanism of circGLIS3 involved in gastric cancer (GC) tumorigenesis has not been elucidated. Methods: The higher expression level of circGLIS3 was identified in GC through RNA sequencing and subsequent tissue verification using Quantitative real-time PCR (qRT-PCR). A series of functional experiments in vitro and in vivo were performed to evaluated the effects of circGLIS3 on tumor growth and metastasis in GC. The interaction and regulation of circGLIS3/miR-1343-3p/PGK1 axis was confirmed by RNA pulldown, western blot, and rescue experiments. RIP and western blot were performed to demonstrate the role of circGLIS3 in regulating phosphorylation of VIMENTIN. We then used qRT-PCR and co culture system to trace circGLIS3 transmission via exosomal communication and identify the effect of exosomal circGLIS3 on gastric cancer and macrophages. Finally, RIP experiments were used to determine that EIF4A3 regulates circGLIS3 expression. Results: CircGLIS3(hsa_circ_0002874) was significantly upregulated in GC tissues and high circGLIS3 expression was associated with advanced TNM stage and lymph node metastasis in GC patients. We discovered that overexpression of circGLIS3 promoted GC cell proliferation, migration, invasion in vitro and in vivo, while suppression of circGLIS3 exhibited the opposite effect. Mechanistically, circGLIS3 could sponge miR-1343-3p and up-regulate the expression of PGK1 to promote GC tumorigenesis. We also found that circGLIS3 reduced the phosphorylation of VIMENTIN at ser 83 site by binding with VIMENTIN. Moreover, it was proven that exosomal circGLIS3 could promote gastric cancer metastasis and the M2 type polarization of macrophages. In the final step, the mechanism of EIF4A3 regulating the generation of circGLIS3 was determined. Conclusion: Our findings demonstrate that circGLIS3 promotes GC progression through sponging miR-1343-3p and regulating VIMENTIN phosphorylation. CircGLIS3 is a potential therapeutic target for GC patients.

Background: Long non-coding RNAs (lncRNAs) plays an important role in the progression of gastric cancer (GC). Their involvement ranges from genetic regulation to cancer progression. However, the mechanistic roles of RP11-789C1.1 in GC are not fully understood. Methods: We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction. A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC cells. In vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line. RNA pull-down unveiled RP11-789C1.1 interacting proteins. Western blot analysis indicated the downstream pathway changes of RP11-789C1.1, and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of oxaliplatin. Results: Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells. Mechanistically, RP11-789C1.1 inhibited checkpoint kinase 1 (CHK1) phosphorylation by binding ataxia-telangiectasia mutated and Rad3 related (ATR), a serine/threonine-specific protein kinase, promoted GC apoptosis, and mediated oxaliplatin sensitivity. Conclusion: In general, we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action, providing a theoretical basis for targeted GC therapy.

Background Circular RNAs (circRNAs) have been proved to play crucial roles in the development of various cancers. However, the molecular mechanism of circGLIS3 involved in gastric cancer (GC) tumorigenesis has not been elucidated. Methods The higher expression level of circGLIS3 was identified in GC through RNA sequencing and subsequent tissue verification using Quantitative real-time PCR (qRT-PCR). A series of functional experiments in vitro and in vivo were performed to evaluated the effects of circGLIS3 on tumor growth and metastasis in GC. The interaction and regulation of circGLIS3/miR-1343-3p/PGK1 axis was confirmed by RNA pulldown, western blot, and rescue experiments. RIP and western blot were performed to demonstrate the role of circGLIS3 in regulating phosphorylation of VIMENTIN. We then used qRT-PCR and co culture system to trace circGLIS3 transmission via exosomal communication and identify the effect of exosomal circGLIS3 on gastric cancer and macrophages. Finally, RIP experiments were used to determine that EIF4A3 regulates circGLIS3 expression. Results CircGLIS3(hsa_circ_0002874) was significantly upregulated in GC tissues and high circGLIS3 expression was associated with advanced TNM stage and lymph node metastasis in GC patients. We discovered that overexpression of circGLIS3 promoted GC cell proliferation, migration, invasion in vitro and in vivo, while suppression of circGLIS3 exhibited the opposite effect. Mechanistically, circGLIS3 could sponge miR-1343-3p and up-regulate the expression of PGK1 to promote GC tumorigenesis. We also found that circGLIS3 reduced the phosphorylation of VIMENTIN at ser 83 site by binding with VIMENTIN. Moreover, it was proven that exosomal circGLIS3 could promote gastric cancer metastasis and the M2 type polarization of macrophages. In the final step, the mechanism of EIF4A3 regulating the generation of circGLIS3 was determined. Conclusion Our findings demonstrate that circGLIS3 promotes GC progression through sponging miR-1343-3p and regulating VIMENTIN phosphorylation. CircGLIS3 is a potential therapeutic target for GC patients.