Ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract, characterized by ongoing intestinal inflammation, epithelial damage, and mucosal injury. Despite the identification of C-C motif chemokine ligand 5 (CCL5) as a key mediator in UC, the precise mechanisms underlying its role in immune activation and inflammation remain unclear. This study aimed to investigate CCL5 as a critical immune modulator in UC, focusing on its effects on immune cell activation, particularly regulatory T cell (Treg) formation, and the molecular pathways involved in these processes. Using the dextran sulfate sodium salt (DSS)-induced UC model and CCL5 knockout (Ccl5-KO) mice, we demonstrated that CCL5 deficiency exacerbates intestinal inflammation during the acute phase of colitis, partly due to impaired interleukin-33 (IL-33)-induced Treg formation. In addition, we observed a positive correlation between CCL5 expression and forkhead box protein 3 (FOXP3) levels in inflamed colon tissues of UC patients, suggesting a role for CCL5 in Treg regulation. Mechanistically, CCL5 deficiency disrupted the PI3K/Akt/NF-κB signaling pathway, resulting in reduced IL-33 expression, which in turn impaired CD4+ T cell activation and FOXP3+ Treg formation via the JAK1/STAT5 pathway. In vivo rescue experiments confirmed that restoring IL-33 signaling could alleviate inflammation and partially recover Treg function. Collectively, these findings highlight CCL5 as a novel immune modulator of Treg formation and immune responses in UC and suggest that targeting CCL5 may offer a promising therapeutic strategy for managing UC and related inflammatory diseases.

Endoscopically obtained gastric mucosal biopsies contain abundant molecular information that could inform Helicobacter pylori (H. pylori) eradication therapy. However, the lack of point-of-care tools for processing solid tissue limits rapid, on-site genotyping, leading to empirical therapy and higher eradication failure rates. Here, we present the SlipChip-based On-site and User-friendly Testing (SCOUT) together with the restriction enzyme-assisted CRISPR/Cas12a (RCut) method for point-of-care genotyping from raw endoscopic gastric biopsies. This fully automated platform enables analysis of key virulence genes and resistance-associated single-nucleotide variants (SNVs) at mutant allele frequencies down to 0.1 %. Results were available within 1 h, enabling actionable molecular profiling during the same endoscopic encounter. In 159 clinical validations, SCOUT showed concordant virulence profiling with quantitative PCR (κ = 0.978) and accurately detected clarithromycin and levofloxacin resistance mutations with up to 100 % sensitivity and specificity. These results demonstrate that SCOUT bridges the gap between diagnostic sampling and informed eradication strategies, providing a scalable framework for point-of-care molecular genotyping.

Abstract Background N6-methyladenosine (m6A) is the most abundant post-transcriptional modification, and METTL16 has recently emerged as a pivotal m6A methyltransferase in cancer. Cholesterol metabolic reprogramming and aberrant MAPK signaling sustain the malignant initiation and progression of colorectal cancer (CRC). However, whether - and how - m6A regulation, particularly by METTL16, interfaces with cholesterol metabolism and downstream oncogenic signaling in CRC remains unknown. Methods Differential expression of METTL16 in CRC was identified through bioinformatic analyses and validated by qRT-PCR, immunoblotting, and immunohistochemistry (IHC). The functional role of METTL16 in CRC progression was examined using in vitro assays and xenograft models. To identify downstream targets, RNA-seq and MeRIP-seq were performed, revealing MSMO1 as a METTL16-regulated gene. The mechanistic basis of the METTL16–MSMO1 axis was investigated through immunoprecipitation-Mass Spectrometry (IP-MS), co-immunoprecipitation (Co-IP), RNA immunoprecipitation (RIP), MeRIP-qPCR, and RNA stability assays. Cholesterol metabolism analyses were conducted to further characterize the metabolic consequences of METTL16–MSMO1 regulation. Results METTL16 was significantly upregulated in CRC and correlated with poor clinical outcomes. Mechanistically, METTL16 enhanced m6A modification of MSMO1, stabilizing its transcript via IGF2BP2 and disrupting intracellular cholesterol homeostasis, which triggered ER stress and activated MAPK-p38/ NF-κB signaling by promoting TAK1/TAB complex formation and TAK1 autophosphorylation, thereby driving CRC progression. Additionally, elevated cholesterol levels further reshaped global m6A methylation patterns and altered methyltransferase expression, suggesting a reciprocal feedback loop between cholesterol metabolism and epigenetic regulation. Conclusions These findings underscore the critical role of the METTL16–MSMO1 axis in driving cholesterol metabolic reprogramming that fuels MAPK-p38/NF-κB oncogenic signaling in CRC, highlighting promising biomarkers and therapeutic targets for improved disease management.

The Notch pathway regulates the homeostasis and tumorigenesis of gastrointestinal epithelium. Given its roles in cancer stem cell capacity and cancer immunity, we hypothesized that Notch activation can predict poor prognosis and resistance to immune checkpoint inhibitors (ICIs) in gastrointestinal adenocarcinoma (GIAC). The mRNA expression and genomic alterations of Notch pathway were characterized in esophagus (ESAD), stomach (STAD), colon (COAD), or rectum (READ) adenocarcinomas from The Cancer Genome Atlas (TCGA) dataset. The prognostic model (mRNA-score) was constructed using the TCGA dataset (the training set) and was validated in 3 independent sets (GSE19417 [ESAD], GSE84437 [STAD], and GSE40967 [COAD]). The associations of the mRNA-score with drug sensitivity, immune cell infiltration, and immunotherapy efficacy were, respectively, analyzed using the Genomics of Drug Sensitivity in Cancer (GDSC) database, the TCGA dataset, and multiple clinical cohorts including GSE165252, PRJEB25780, IMvigor210, and CheckMate-009/010/025. Notch pathway genes exhibited conserved genomic/transcriptomic features across four GIAC subtypes. Three pan-GIAC clusters were determined by unsupervised clustering, and the cluster with higher expression of the Notch pathway genes had shorter overall survival (OS), immunosuppressive microenvironment, and higher scores of the signatures concerning angiogenesis, cell cycle, PI3K-AKT-mTOR, TGF-β, glycolysis, etc. A prognostic algorithm (mRNA-score) was constructed, which was correlated with poor OS in the training set (TCGA, P < 0.001) and three validation sets (GSE19417, P = 0.025; GSE84437, P = 0.001, GSE40967, P = 0.007). A high mRNA-score was linked with more “resting”/ “anti-inflammatory” rather than “activated”/ “pro-inflammatory” tumor-infiltrating immune cells and ICI resistance in GIACs (GSE165252, P = 0.047; PRJEB25780, P = 0.047) and other solid tumors such as urothelial carcinoma and clear cell renal cell carcinoma. Our findings demonstrate the utility of the Notch pathway in predicting prognosis and ICI resistance. Further studies are warranted to explore the efficacy of Notch inhibitors as immunotherapeutic adjuvants to overcome ICI resistance.

Dysregulation of RNA N6-methyladenosine (m6A) modification in intestinal epithelial cells (IECs) compromises intestinal homeostasis, which is critical for maintaining gastrointestinal functions, immunity, and barrier integrity in inflammatory bowel disease (IBD). Here we explored the role of m6A modification, particularly through methyltransferase like 3 (METTL3), in IBD pathology and the apoptosis of intestinal stem cells (ISCs). Reduced m6A RNA methylation and METTL3 expression were detected in IBD tissues, which correlated with increased ISC apoptosis and spontaneous enteritis in METTL3-deficient models; mechanistically, Mettl3 depletion increased TRADD expression in a m6A-dependent manner, thereby augmenting the TNF-induced apoptosis pathway, whereas pharmacological inhibition of TRADD ameliorated the apoptotic phenotype in METTL3-deficient models and improved survival rates in the enteritis mouse model, suggesting a novel therapeutic avenue for IBD management. Collectively, METTL3-mediated m6A RNA methylation plays a pivotal role in maintaining intestinal homeostasis and is activated in ISCs to mitigate the hyperactivity of endogenous inflammatory signals; by modulating TRADD transcript metabolism, METTL3 limits excessive ISC apoptosis, providing insights into IBD pathogenesis and treatment strategies.

Colorectal cancer (CRC), one of the common malignant tumors, ranks third in incidence and second in mortality, posing a seriously threat to human health. CRC presents major clinical challenges in terms of early and accurate diagnosis, precise surgical resection, and effective treatment monitoring. In CRC research, vascular endothelial growth factor receptor 2 (VEGFR-2) has emerged as a key therapeutic target due to its important role in tumor angiogenesis. Abnormal expression of VEGFR-2 is closely related to the occurrence, development and prognosis of CRC. Notably, VEGFR-2 expression remains minimal during the colitis stage but markedly increases during the adenoma and carcinogenesis stages. Therefore, VEGFR-2 represents an ideal target for diagnostic probes in CRC. In this study, we developed a near-infrared fluorescence probe specifically targeting VEGFR-2. Reasonable molecular design and structural optimization endow the probe with excellent pharmacokinetic properties and specific VEGFR-2-targeting ability. The feasibility and application potential of the fluorescent probe in tumor diagnosis and surgical resection were verified by different animal models. This study demonstrates the feasibility of targeted VEGFR-2 fluorescence imaging technology for the diagnosis and surgical navigation of subcutaneous and orthotopic CRC models at both cellular and animal levels. This fluorescent probe, specifically targeting VEGFR-2, offers new opportunities for CRC research.

This study aims to investigate the role of LACTB (Serine beta-lactamase-like protein) in colorectal cancer (CRC) cell stemness and differentiation. In the current study, we assessed LACTB expression levels by analyzing data from database and our collected CRC samples. The association between LACTB level and clinical characteristics was further explored. HT29 and SW480 cell lines were employed for the in vitro experiments. A series of experiments were performed to investigate protein-protein and protein-DNA interactions. KLF5 knockout cell lines were established using CRISPR/Cas9 double-knockout plasmids. Acetylated K369 mimic KLF5 and deacetylated K369 mimic KLF5 were constructed to investigate the function of K369 acetylation. Finally, the functional significance of these findings was validated in a xenograft model. Our results showed that compared with adjacent normal tissues, LACTB exhibited low expression levels in CRC tissues, with particularly low levels observed in poorly differentiated carcinomas. Functional studies revealed that LACTB overexpression promoted cell differentiation while suppressing cell stemness. Mechanistically, LACTB exerted its function by destabilizing OMA1 protein, thereby modulating OPA1-mediated mitochondrial fusion. Further experiments identified KLF5 as a transcriptional repressor of LACTB, with its suppressive effect dependent on acetylation at lysine 369 (K369). An acetylated-mimic KLF5 mutant exhibited enhanced capacity to promote stemness and block differentiation, whereas a deacetylation-mimic form displayed opposite effects. Collectively, our findings revealed that acetylated KLF5 inhibited LACTB transcription, which subsequently orchestrates mitochondrial dynamics through the OMA1/OPA1 axis, ultimately governing CRC cell stemness, differentiation and tumor progression.

PURPOSE:Cancer cells rely on serine biosynthesis for growth, but its regulation in colorectal cancer (CRC) remains not well understood. This study identifies the m5C methyltransferase NSUN2 (NOP2/Sun domain family, member 2) as a key regulator of serine biosynthesis, revealing a novel mechanism driving CRC progression. METHODS:The expression and prognostic value of NSUN2 were evaluated using bioinformatics analyses and immunohistochemistry (IHC) assays. The effects of NSUN2 on cellular serine biosynthesis, intracellular reactive oxygen species (ROS) levels, and apoptosis levels were analyzed both in vitro and in vivo. Additionally, RNA sequencing, Methylated RNA Immunoprecipitation sequencing (MeRIP-seq), RNA immunoprecipitation (RIP), and RNA stability assays were utilized to screen and validate the association between NSUN2 and phosphoglycerate dehydrogenase (PHGDH). RESULTS:NSUN2 was found to be highly expressed in CRC and associated with poor patient survival. PHGDH, a direct downstream target of NSUN2, plays a crucial role in NSUN2-mediated serine biosynthesis. Furthermore, inhibition of NSUN2 significantly reduced the intracellular NADH/NAD+ and NADPH/NADP+ ratios, leading to an increase in ROS levels and apoptosis levels, thereby inhibiting CRC progression. Additionally, NSUN2 enhances PHGDH expression and mRNA stability by binding to the "reader" protein m5C-Aly/REF export factor (ALYREF). CONCLUSIONS:This study identified a novel NSUN2/ALYREF/m5C-PHGDH axis might be promising therapeutic targets for CRC.

Inducible Co-Stimulator (ICOS), as a T-cell–specific costimulatory receptor that enhances T-cell responses to foreign antigens, plays a crucial role in cancer immunity. However, its role in MSS/pMMR colorectal cancer (CRC) remains unclear. In this study, we demonstrated that ICOS expression decreases as the tumor stages advance and that high ICOS expression is associated with a favorable prognosis in MSS/pMMR CRC. Mechanistically, ICOS promoted the secretion of IFN-γ, TNF-α, and IL-12 in CD4+ T cells through the Akt/STAT1/T-bet axis, leading to the inhibition of MSS/pMMR-CRC-cell proliferation. Importantly, ICOS+ CD4+ T cells enhanced tumor responses to anti-PD-1 therapy in MSS/pMMR CRC. In conclusion, this study revealed that ICOS mediates antitumor immunity by promoting the secretion of cancer-suppressive cytokines. It also suggests that activation of ICOS serves a potential therapeutic strategy for MSS/pMMR CRC.

Growth differentiating Factor 15 (GDF15) is linked to several cancers, but its effect on chemoresistance in colorectal cancer (CRC) remains unclear. Here, we investigated the role of GDF15 in the chemotherapeutic response of CRC patients to oxaliplatin (L-OHP). GDF15 levels in serum and tumour tissues were detected in CRC patients have received L-OHP-based neoadjuvant chemotherapy. The effects of GDF15 neutralization or GDF15 knockdown on cell proliferation, apoptosis and intracellular reactive oxygen species (ROS) levels were analysed in vitro and in vivo. Co-immunoprecipitation (Co-IP), Chromatin Immunoprecipitation (ChIP) and luciferase reporter assays were used to explore the interaction between GDF15 and Nrf2. In this study, we found that GDF15 alleviates oxidative stress to induce chemoresistance of L-OHP in CRC. Mechanically, GDF15 posttranscriptionally regulates protein stability of Nrf2 through the canonical PI3K/AKT/GSK3β signaling pathway, and in turn, Nrf2 acts as a transcription factor to regulate GDF15 expression to form a positive feedback loop, resulting in the maintenance of redox homeostasis balance in CRC. Furthermore, a positive correlation between GDF15 and Nrf2 was observed in clinical CRC samples, and simultaneous overexpression of both GDF15 and Nrf2 was associated with poor prognosis in CRC patients treated with L-OHP. Simultaneous inhibition of both GDF15 and Nrf2 significantly increases the response to L-OHP in an L-OHP-resistant colorectal cancer cells-derived mouse xenograft model. This study identified a novel GDF15-Nrf2 positive feedback loop that drives L-OHP resistance and suggested that the GDF15-Nrf2 axis is a potential therapeutic target for the treatment of L-OHP-resistant CRC.

The fungal microbiota is an important component of the complex multikingdom microbial community colonizing the mammalian gastrointestinal tract and has an important role in immune regulation. However, how fungi regulate inflammatory bowel disease (IBD) is poorly understood. This study found that intestinal fungi regulate immune responses in IBD. Antibiotic-mediated depletion of fungi facilitated the development of IBD. Fungi greatly enhanced oxidative phosphorylation (OXPHOS) by enhancing glutaminolysis. Mechanistically, we found that fungi could activate the dectin-1-Syk- NF-κB signaling pathway to promote the expression of key enzymes and transporters involved in glutaminolysis. In summary, our findings reveal that fungal interactions in the human gut could be a promising therapeutic target for IBD.

目的:探讨lncRNA牛磺酸上调基因1(taurine upregulated gene 1,TUG1)与结直肠癌临床病理因素的相关性及临床意义,以及其促进结直癌细胞增殖和侵袭的生物学功能.方法:实时定量PCR(real-time quan-titative PCR,RT-qPCR)检测结直肠癌组织TUG1的表达水平,并采用卡方检验分析TUG1表达水平与临床资料的相关性.Kaplan-Meier生存曲线和log-rank检验分析TUG1表达水平与结直肠癌预后的相关性.CCK8实验和Transwell实验检测过表达和敲低TUG1后的结直肠癌细胞增殖或侵袭能力的变化.结果:TUG1在结直肠癌组织中表达水平明显升高(P＜0.05);TUG1表达水平与肿瘤大小、CEA水平、淋巴结转移、远处转移以及TNM分期密切相关(P＜0.05).Kaplan-Meier生存曲线和log-rank检验提示,TUG1表达水平越高,结直肠癌患者预后越差(P＜0.05).CCK8和Transwell实验结果表明,与对照组相比,pcDNA3.1-TUG1组结直肠癌细胞中TUG1表达水平明显增高(P＜0.05),细胞增殖活性和侵袭数目增多(P＜0.05);而siRNA-TUG1组结直肠癌细胞中TUG1表达水平明显降低(P＜0.05),细胞增殖活性和侵袭数目减少(P＜0.05).结论:TUG1在结直肠癌组织中呈高表达,且TUG1表达水平越高,患者预后越差.并且,lncRNA TUG1促进结直肠癌细胞的增殖和侵袭能力.

目的:探讨腹腔镜直肠癌术中肠系膜下动脉根部淋巴结(No.253淋巴结)的临床病理特点、转移的危险因素及其对患者预后的影响.方法:回顾分析2017年1月至2018年12月行腹腔镜直肠癌手术的432例患者的临床病理资料,并对肠系膜下动脉根部淋巴结转移的影响因素进行单因素与多因素分析.术后随访,进行3年总生存率与无病生存率的log-rank检验分析.结果:肠系膜下动脉根部淋巴结转移率为6.48％(28/432),No.253淋巴结阳性病例均有癌旁淋巴结转移.肠系膜下动脉根部转移患者的3年总生存率(57.14％vs.86.38％,P<0.001)、3年无病生存率(50.00％vs.81.43％,P<0.001)均低于无转移的患者.单因素分析显示,肿瘤距肛缘>7 cm(P=0.021)、CEA>5 ng/mL(P=0.006)、肿瘤直径>5 cm(P=0.039)、T3～T4分期(P=0.030)、低分化(P=0.026)、非管状腺癌(P=0.005)是No.253淋巴结转移的危险因素.Logistic多因素分析进一步显示,CEA>5 ng/mL(P<0.001)、T3～T4分期(P=0.038)、低分化(P=0.017)、非管状腺癌(P<0.001)是No.253淋巴结转移的独立危险因素.结论:CEA>5 ng/mL、T3～T4分期、低分化、非管状腺癌是No.253淋巴结转移的独立危险因素.对于有上述独立危险因素的患者,建议行No.253淋巴结规范化清扫,以达到更好的肿瘤学效果.

There were still some technical issues,such as surgical approach,and lymphatic dissection,which were still under debate.Based on clinical practice,the following recommendations are proposed:（1） Determine the type of inferior mesenteric artery through abdominal CT angiography before surgery,and use the intermediate combined cephalic approach for surgery,which is conducive to accurate preservation of LCA.（2）Standardized dissection of No.253 lymph nodes is necessary during the preservation of LCA.（3） The use of the "6-321Risk Assessment Scale for Anastomotic Leakage after Low Rectal Cancer Surgery" can accurately predict the occurrence of anastomotic leakage after low rectal cancer surgery,providing a direct and beneficial reference standard for whether preventive stoma should be performed simultaneously during surgery.

Our previous work suggested that high SIRT1 expression by cancer cells predicted a poor colorectal cancer (CRC) prognosis, but its role in the tumor microenvironment was unclear. Here, we examined tumor-infiltrating lymphocytes (TILs) in CRC expressing different levels of SIRT1. We also established a co-culture system with monocytes, CD8+ T cells and patient-derived tumor organoids (PDOs) to study the relationships between immune cells and cancer cells. The percentage of CD8+ T cells was decreased and the percentage of macrophages was increased in SIRT1-high (SIRT1-hi) CRC. Co-culture results showed that tumor-associated macrophages (TAMs) from SIRT1-hi CRC inhibited the proliferation and anti-tumor activity of CD8+ T cells. Importantly, SIRT1-hi CRC were shown to modulate the migration and the activity of TAMs. RNA sequencing revealed that CD14+ monocytes in SIRT1-hi patients expressed higher levels of CXCR4. Mechanistically, SIRT1 expression was shown to promote CXCL12 expression by inhibiting the acetylation of p53. Our findings indicate that SIRT1 in CRC induces TAM migration through the CXCR4/CXCL12 pathway, and inhibits the proliferation and activity of CD8+ T cells, resulting in promotion of CRC progression.

目的:探讨miR-106b-5p对结直肠癌(colorectal cancer,CRC)细胞增殖、迁移与侵袭的影响以及其作用机制.方法:实时荧光定量PCR检测miR-106b-5p在CRC组织与相应的癌旁组织、永生化的肠上皮细胞以及肠癌细胞中的表达量;CCK8实验检测DLD1细胞增殖能力;细胞划痕实验检测DLD1细胞的迁移能力;Transwell实验检测DLD1细胞的侵袭能力;生物信息学预测miR-106b-5p的下游靶基因;运用双荧光素酶报告基因实验验证细胞周期蛋白D1(cyclin D1,CCND1)是miR-106b-5p的靶基因;RNA结合蛋白免疫沉淀实验进一步验证miR-106b-5p与CCND1之间的相互作用;运用蛋白免疫印迹实验检测组织和细胞中CCND1的蛋白表达水平.结果:与癌旁组织相比较,miR-106b-5p在结直肠癌组织中表达量降低(P<0.05);与永生化的肠上皮细胞相比较,miR-106b-5p在结直肠癌细胞中表达量降低(P<0.05);CCK8、细胞划痕实验以及Transwell实验表明,在DLD1细胞中,过表达miR-106b-5p能显著抑制细胞的增殖、迁移和侵袭能力(P<0.05);运用Starbase数据库预测miR-106b-5p下游靶基因为CCND1,miR-106b-5p作用于CCND1的3'-UTR区域,双荧光素酶报告基因实验与RNA结合蛋白免疫沉淀实验验证了miR-106b-5p与CCND1之间的相互作用;CCND1在结直肠癌组织与细胞中明显高表达(P<0.05),在DLD1细胞中过表达miR-106b-5p明显抑制CCND1的表达(P<0.05).结论:miR-106b-5p在CRC组织和细胞中表达降低,miR-106b-5p通过抑制CCND1表达抑制细胞增殖、迁移及侵袭.

目的 分析腹腔镜低位直肠癌前切除术肠系膜下动脉高位结扎和低位结扎对低位前切除综合征(LARS)的影响.方法 采用回顾性队列研究方法,收集2019年1月至2020年8月期间在上海交通大学医学院附属仁济医院胃肠外科腹腔镜低位直肠癌前切除术的282例病人的临床资料.根据术中是否保留左结肠动脉(LCA),分为低位结扎组(n=126)和高位结扎组(n=156),比较两组术后LARS发生率和严重程度,并通过单因素和多因素分析LARS的危险因素.结果 对126例低位结扎病人术后3个月,6个月和12个月的影像学随访发现,117例(92.86％)病人术后左结肠动脉通畅,仅9例(7.14％)病人术后左结肠动脉闭塞.282例病人术后3个月,6个月,12个月 LARS 总发生率为:57.44％(162/282),42.91％(121/282),34.04％(96/282);术后3个月后无新发LARS病例.低位结扎组的术后3个月、6个月LARS的发生率明显低于高位结扎组(46.83％vs.66.03％,P=0.00;35.71％vs.48.72％,P=0.03).而术后12个月低位结扎组和高位结扎组LARS发生率差异无统计学意义(25.40％vs.34.62％,P--0.09).通过单因素分析,发现肿瘤大小＞3.5 cm(P=0.01)、非专业化水平(P=0.01)、高位结扎(P=0.03)、吻合口距齿状线距离≤2 cm(P=0.01)是LARS的危险因素;进一步通过多因素分析,发现高位结扎(P=0.02)、非专业化水平(P=0.01)、吻合口距齿状线距离≤2cm(P=0.01)是LARS的独立危险因素.结论 腹腔镜低位直肠癌前切除术中保留左结肠动脉可以降低术后LARS的发生率,尤其是轻度LARS病人,其近期疗效较满意,有临床推广价值.

Background: Ulcerative colitis (UC) is a well-known risk factor for developing colitis-associated colorectal cancer (CAC). However, the molecular mechanism of the pathogenesis of CAC remains unclear. This study aimed to explore candidate genes involved in the tumorigenesis of CAC. Methods: GSE75214 and the Cancer Genome Atlas Program (TCGA) dataset were used to analyze the differentially expressed genes (DEGs) in UC and colorectal cancer (CRC), respectively. Survival-hub genes were identified from these DEGs by sequentially constructing a protein-protein interaction network, selecting hub genes, and conducting survival analysis. Regulatory signatures were also predicted on these genes through the online database. Apc (min/+) and UC mice models were used to validate the expression of the above-predicted molecules. Gene set enrichment analysis and CIBERSORT were performed to explore the enriched molecular pathways and associated tissue-infiltrating immune cells of genes. Results: Here, 376 common DEGs were identified from the GSE75214 and TCGA datasets. Through survival-hub gene selection and in vivo experiments, we confirmed that CXCL10 and CXCL11 were significantly upregulated in UC and CRC. We also proved that miR-34a-5p and miR-203a-5p were potential regulators of CXCL10 and CXCL11. Meanwhile, CXCL10 and CXCL11 may activate the JAK-STAT signaling pathway via the interaction with cytokine receptors in UC. Furthermore, CXCL10 and CXCL11 were positively associated with the tissue infiltration of proinflammatory M1 macrophages in UC and CRC. Conclusion: CXCL10 and CXCL11 may act as the candidate genes involved in the tumorigenesis of CAC and potential therapeutic targets to prevent the development of CAC from UC.

Background Anastomotic leakage (AL) is one of most severe postoperative complications following low anterior resection (LAR) for rectal cancer, and has an adverse impact on postoperative recovery. The occurence of AL is associated with several factors, while few studies explored the role of intracorporeal barbed suture reinforcement in it. Methods Consecutive cases underwent laparoscopic LAR for rectal cancer from Mar. 2018 to Feb. 2021 in our center were retrospectively collected. Cases were classified into the intracorporeal barbed suture reinforcement group and the control group according to whether performing intracorporeal reinforcement with barbed suture, and AL incidences were compared between two groups. Propensity score matching (PSM) was then performed based on identified risk factors to reduce biases from covariates between two groups. AL incidences in the matched cohort were compared. Results A total of 292 cases entered into the study, and AL incidences were significantly lower in the intracorporeal barbed suture reinforcement group compared with the control group (10.00% vs 2.82%, P = 0.024). Sex, BMI, preoperative adjuvant chemoradiotherapy and anastomotic level were chose for PSM analyses based on previous studies. In the matched cohort, the AL incidences were still significantly lower in the intracorporeal barbed suture reinforcement group (10.57% vs 2.44%, SD = 0.334). Conclusions Intracorporeal barbed suture reinforcement is associated with low AL incidences after laparoscopic LAR for rectal cancer, which is a potential procedure for reducing AL and worthy of application clinically.

Adhesive intestinal obstruction is the most common type of ileus, and conserva-tive treatment serves as its preferred treatment option. In the course of conservative treatment, gastrointestinal decompression will relieve symptoms, prevent ileus progression and promote gas-trointestinal function recovery, which has significant clinical effects. Currently, decompression effects of nasointestinal tubes and nasogastric tubes are controversial. There is a previous Meta-analysis evaluating decompression effects of these two methods, but this analysis includes non-randomized controlled trial and lacks research about Chinese patients. Therefore, the authors con-duct a Meta-analysis to evaluate decompression effects of nasointestinal tubes versus nasogastric tubes for adhesive intestinal obstruction.