Jianbin Xiang

HDAC3 is highly expressed in colorectal cancer (CRC) and associated with poor prognosis. This study reveals that HDAC3 deletion dually regulates chemokine expression through epigenetic mechanisms, promoting CD8⁺ T cell infiltration (via CXCL10) on one hand, while enhancing the recruitment of myeloid-derived suppressor cells (MDSCs) (via CXCL1/2/3/5) on the other. The latter, mediated through CXCR2 signaling, counteracts the intrinsic anti-tumor effect of HDAC3 deletion. We further demonstrate that combining a CXCR2 inhibitor effectively blocks MDSC infiltration and significantly enhances the immunotherapeutic efficacy mediated by HDAC3 deletion. This study systematically elucidates the “double-edged sword” role of HDAC3 in the CRC immune microenvironment and provides a theoretical and experimental basis for an HDAC3/CXCR2 dual-targeting therapeutic strategy.

Background: Colorectal cancer (CRC) outcomes remain heterogeneous despite therapeutic advances, posing challenges to precise prognostic stratification. Post-translational modifications (PTMs) critically regulate protein function, tumor microenvironment (TME) crosstalk, and CRC progression, while most existing studies only focus on single PTM types and PTM signals are rarely integrated into CRC risk models. Methods: We built a post-translational modification–related risk signature (PTMRS) model by screening post-translational modification–related (PTM-related) genes associated with prognosis in The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression project (GTEx)datasets, then benchmarking 101 modeling strategies to select a Cox partial least squares framework. External validation was conducted across multiple independent cohorts and immunotherapy datasets. Single-cell RNA sequencing (scRNA-seq) data were used to calculate cell type–specific scores for the PTMRS and to perform CellChat-based analyses of cell–cell communication. To investigate mechanism, we targeted platelet-derived growth factor receptor-β (PDGFRβ) in human colonic fibroblasts and assessed CRC-cell responses to their conditioned media. Results: PTMRS robustly stratified overall survival across cohorts and aligned with an immune-cold, stroma-enriched phenotype. PTMRS was associated with pathways related to antigen presentation, protein homeostasis, and other processes within the CRC TIME. ScRNA-seq analysis further showed that PTMRS scores influenced intercellular communication between CRC cells and immune cells. PDGFRB was validated as a core node within the PTMRS network: activation of PDGFRβ in human colonic fibroblasts promoted CRC cell proliferation and migration, whereas sunitinib attenuated and reversed these effects. Conclusions: We established a post-translational modification–related risk signature (PTMRS) that robustly stratifies CRC prognosis and links tumor-intrinsic programs with features of the TIME. Higher PTMRS scores, particularly in tumors with PDGFRB enrichment, were associated with a stroma-rich, immune-cold phenotype. Experimental validation highlighted PDGFRβ in colonic fibroblasts as a stromal hub whose activation promotes CRC cell proliferation and migration. These findings suggest that PTMRS may help identify patients who could benefit from combining immunotherapy with therapies targeting PDGFRβ or other PTM-related pathways. Further validation in in vivo models and prospective clinical cohorts is needed.

Background: This study aimed to comparatively evaluate the tissue healing characteristics of High-Frequency Electric Welding (HFEW) versus conventional suture techniques in intestinal side-to-side anastomosis using an animal model. Materials and methods: Intestinal side-to-side anastomoses were performed in New Zealand White rabbits using HFEW and hand-sewn techniques. Intraoperative assessment focused on procedure duration, hemostasis, and immediate anastomotic strength. Postoperative monitoring tracked vital signs, physiological parameters, healing progression (assessed via burst pressure), histopathological features, and inflammatory cell infiltration. Results: HFEW application reduced surgical duration and postoperative bleeding. Healing progression was comparable between HFEW and Suture groups. At 1 week postoperatively, vital signs and tissue strength normalized in experimental animals, with necrotic tissue replaced by regenerated tissue; Suture group specimens exhibited elevated inflammatory cell infiltration. By week 2, tissue strength further improved, inflammation subsided, and tissue morphology advanced. At 4 weeks, pathological structures in both HFEW and Suture groups closely resembled normal tissue. Compared with sutures, HFEW has advantages in terms of operating time and blood loss. During the postoperative healing phase, HFEW can effectively reduce the inflammatory response and accelerate healing. Conclusions: Postoperative healing with HFEW-based intestinal repair demonstrates comparability to manual suturing, while exhibiting reduced complication rates – offering residue-free foreign body anastomosis solution for laparoscopic surgery.

Alternative polyadenylation (APA) is critical for shaping transcriptome diversity by generating mRNA isoforms that differ in the length of their 3′untranslated region (3′UTR). APA dysregulation, a defined feature of tumorigenesis, remains poorly understood in colorectal cancer (CRC). Here, CRISPR/Cas9 screening identifies APA regulator NUDT21 as a key driver of CRC progression. NUDT21 is overexpressed in CRC tumors and correlates with poor prognosis in CRC patients. Genetic ablation of NUDT21 impairs CRC cell proliferation and triggers CD8 ⁺ T cell anti‐tumor response through disrupting cholesterol biosynthesis, leading to delayed tumor progression in syngeneic mouse models. Mechanistically, NUDT21 promotes the generation of cyclin‐dependent kinase 19 (CDK19) mRNA isoforms with long 3′UTR by directing usage of distal polyadenylation sites. The long 3′UTR facilitates the export of CDK19 transcripts to the cytoplasm and supports their efficient translation, with no impact on their stability. Truncation of the long 3′UTR of Cdk19 recapitulates cholesterol biosynthesis and proliferative impairments, as well as the enhanced anti‐tumor CD8 ⁺ T cell activity observed upon NUDT21 depletion, whereas CDK19 overexpression rescues these phenotypes. The findings establish the NUDT21‐CDK19 axis as a central hub integrating APA manner, cholesterol metabolic reprogramming, and immune evasion in CRC, unveiling potential therapeutic opportunities.

Background Functional outcomes and quality of life (QoL) of transverse coloplasty pouch (TCP) in intersphincteric resection (ISR) for ultralow rectal cancer remain poorly understood. Methods A prospective analysis was conducted on patients who received ISR treatment from January 2020 to May 2022. Patients were divided into TCP and straight coloanal anastomosis (SCAA) groups. Comparisons were made for low anterior resection syndrome (LARS) score, Wexner incontinence score (WIS), Kirwan’s incontinence score, visual analog scale (VAS), and fecal incontinence quality of life (FIQL) questionnaire at 3, 6, and 12 months post ileostomy closure. Additionally, anorectal manometry outcomes were compared pre ileostomy closure. Results A total of 75 patients were included, with 25 in the TCP group and 50 in the SCAA group. At 3, 6, 12 months post ileostomy closure, the TCP group showed significantly lower LARS (31, 30, 28; p = 0.033, 0.044, 0.019, respectively), WIS (11.04, 9.92, 7.32; p = 0.025, 0.043, 0.007, respectively), and Kirwan’s incontinence scores (p = 0.044, 0.033, 0.022). Additionally, the TCP group showed higher VAS (5, 6, 7; p = 0.004, 0.006, 0.005, respectively) and FIQL summary scores (2.67, 2.79, 2.86; p = 0.001, 0.002, 0.004, respectively). Prior to ileostomy closure, the rectal first sensation and maximum tolerance volumes were significantly higher in the TCP group compared to the SCAA group (22 ml vs. 20 ml, 51.56 ml vs. 34.52 ml; p = 0.019, 0.038, respectively). There were no significant differences in postoperative complications or recurrence rates between the groups. Conclusions TCP is a safe technique, which may improve bowel function and QoL in ISR patients with low rectal cancer within 1 year.

Background: The precise anatomical plane and the pathological significance of circumferential resection margin integrity for ultralow rectal cancer remain inadequately defined. This article investigates the spatial architecture of the intersphincteric complex (ISC) and its clinical implications in intersphincteric space dissection for ultra-low rectal cancer. Materials and methods: Formalin-fixed hemipelvis specimens ( n = 37) from the laboratory of applied surgical anatomy were analyzed by macroscopic dissection and multiplexed immunofluorescence to characterize anatomical features of the ISC. Additionally, patients diagnosed with ultra-low rectal cancer ( n = 221) between 2019 and 2024 were enrolled prospectively. Primary endpoints for the patient group included disease free survival, local recurrence free survival and overall survival. Secondary endpoints involved the assessment of anorectal function using prospective questionnaires. Results: Anatomy and histologic research introduced the concept of the intersphincteric complex. Proportion of patients with tumor metastasis in the intersphincteric complex was 61/197 (30.96%), indicating that the intersphincteric complex represented a potential site for metastasis in ultra-low rectal cancer. Complete intersphincteric complex excision was associated with favorable disease-free survival (HR, 0.382 [95% CI, 0.187–0.781]; P = 0.008) and local recurrence-free survival (HR, 0.251 [95% CI, 0.085–0.741]; P = 0.012) in patients and no significant differences was found among three subgroups concerning Wexner scores and LARS scores. Conclusion: A systematic anatomical analysis of the intersphincteric complex clearly elucidated key structures facilitating for ultralow rectal cancer. The intersphincteric complex is frequently a site for tumor metastasis and complete intersphincteric complex excision conferring favorable prognosis in patients with ultralow rectal cancer.

Objective: To evaluate the effects of 2 intersphincteric space (ISS) dissection approaches for intersphincteric resection (ISR) on perioperative safety, oncological prognosis, and anal function. Background: The dissection of ISS is a crucial aspect of ISR, yet the outcomes associated with various ISS dissection approaches remain uncertain. Methods: Data were retrospectively collected from 314 patients with rectal cancer who underwent ISR at 5 Chinese tertiary referral medical institutions from January 2015 to December 2020. ISS dissection was performed using 1 of the 2 avenues: the complete transabdominal approach (CTA) and the transabdominal-perineal transanal approach (TPTA). The primary endpoints were 3-year overall survival (OS) and disease-free survival (DFS) rates. The secondary endpoints were postoperative anal function assessed by questionnaires. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to match the clinicopathological characteristics of patients from both cohorts. Results: After PSM, 140 patients were successfully matched in the CTA and TPTA groups. There were no statistically significant differences between the groups in terms of perioperative complication rates, 3-year OS/DFS, and Wexner incontinence scores within 3 years after ileostomy reversal surgery (P > 0.05). However, the CTA group demonstrated less surgical time and superior low anterior resection syndrome (LARS) scores compared with the TPTA group (P < 0.05). Similar outcomes were observed after conducting IPTW adjustment. Conclusions: CTA and TPTA showed similar efficacy regarding perioperative safety and oncological outcomes. However, the CTA approach demonstrated a clear superiority in the LARS score.

Acquired resistance poses a significant obstacle to the effectiveness of platinum-based treatment for cancers. As the most abundant antioxidant, glutathione (GSH) enables cancer cell survival and chemoresistance, by scavenging excessive reactive oxygen species (ROS) induced by platinum. Therapeutic strategy targeting GSH synthesis has been developed, however, failed to produce desirable effects in preventing cancer progression. Thus, uncovering mechanisms of rewired GSH metabolism may aid in the development of additional therapeutic strategies to overcome or delay resistance. Here, we identify upregulation of long noncoding RNA (lncRNA) GDIL (GSH Degradation Inhibiting LncRNA) in platinum resistant colorectal cancer (CRC) and ovarian cancer cells compared with parental ones. High expression of GDIL in resistant CRC is associated with poor survival and hyposensitivity to chemotherapy. We demonstrate that GDIL boosted GSH levels and enhances clearance of ROS induced by platinum. Metabolomic and metabolic flux analysis further reveals that GDIL promotes GSH accumulation by inhibiting GSH degradation. This is attributed by downregulation of CHAC1, an enzyme that specifically degrades intracellular GSH. Mechanistically, GDIL binds and re-localizes the nuclear protein XRN2 to the cytoplasm, where GDIL further serve as a scaffold for XRN2 to identify and degrade CHAC1 mRNA. Suppression of GDIL with selective antisense oligonucleotide, restored drug sensitivity in platinum resistant cell lines and delayed drug resistance in cell line- and patient-derived xenografts. Thus, lncRNA GDIL is a novel target to promote GSH degradation and augment platinum therapy.

Emphysematous cystitis (EC) refers to a rare form of complicated urinary tract infection (UTI), which is typically observed in elderly females with severe diabetes mellitus. EC was triggered by bacteria, producing gas filled cysts in the bladder wall and lumen, the most common of which are Escherichia coli and Klebsiella pneumoniae. Since EC could be potentially life-threatening, severe form of EC (like septic shock) can cause gangrenous cystitis (GC). This case report describes an 85-year-old female patient with type 2 diabetes mellitus (DM) who presented with EC and bladder gangrene due to the growth of Candida glabrata in urine. Our case describes patient’s progression in detail, ranging from the initial clinical manifestations to specific management actions, which may provide new insights and ideas for the diagnosis and treatment of such disease.