Abstract Purpose To compare the surgical outcomes between patients with and without Persistent Descending Mesocolon (PDM) undergoing colorectal resection. Methods A systematic search of electronic databases (PubMed, Embase, Cochrane Library and Web of Science) was conducted for studies published from inception to October 13, 2025. Statistical heterogeneity was assessed using the I2 statistic and the Cochran’s Q test (with a significance level of P < 0.1). High heterogeneity was considered when I2 > 50%, in which case a random-effects model was applied. For studies with I2 ≤ 50%, a fixed-effects model was used, and a P-value < 0.05 was considered statistically significant. All analyses were performed using Stata software (version 18.0). The registration ID of this current meta-analysis on PROSPERO is CRD420251166710. Results Six observational studies, encompassing a total of 2437 patients (PDM: n=154; Non-PDM: n=2283), were included in the final analysis. Patients in the PDM group had a significantly longer operative time (MD: 28.43minutes, 95% CI: 2.71 to 54.16, p = 0.03). However, no significant difference was found in intraoperative blood loss and postoperative hospital stay between the PDM group and the Non-PDM group. Furthermore, no significance was found in overall complications (OR=1.14, 95% CI = 0.60 to 2.16, P = 0.69). Conclusion The presence of PDM is associated with increased surgical complexity, evidenced by longer operative times. Surgeons should be aware of this anatomical variant during preoperative planning for colorectal procedures. No statistically significant differences were observed in postoperative outcomes between PDM and Non-PDM groups.

The purpose of this study was to analyze whether advanced glycation end products (AGEs) and their receptors had an impact on the development and prognosis of colorectal cancer (CRC). This study examined the databases of PubMed, Embase, Cochrane Library databases and CNKI up to 7 February 2024 for cohort studies assessing the association between AGEs and their receptors, including receptor for advanced glycation end products (RAGE) and soluble receptor for advanced glycation end products (sRAGE) on the development and prognosis of CRC. The meta-analysis included eight studies with a total of 8,278 participants. It demonstrated that sRAGE expression was significantly lower in CRC patients compared to controls. In contrast, no significant differences were found in the expression levels of RAGE or AGEs between CRC patients and controls. Overall survival was not significantly associated with RAGE expression levels. Subgroup analysis indicated that the inverse association between sRAGE and CRC was significant in the general population but not observed among diabetic patients. Low sRAGE expression was associated with an increased risk of CRC development, whereas RAGE and AGEs were not associated with the development and prognosis of CRC.

ABSTRACT Background Colorectal cancer (CRC) is a major global health problem, ranking as the third most commonly diagnosed cancer and the second leading cause of cancer‐related deaths. This study aimed to elucidate the role and underlying molecular mechanism of the Regenerating Islet‐Derived Protein 1 Alpha (REG Iα)/Endothelin Receptor B (EDNRB) axis in CRC malignant progression. Methods A nude mouse xenograft model and human CRC cell lines were used to investigate the REG Iα/EDNRB axis. RNA‐sequencing (RNA‐seq) was employed to identify downstream targets following REG Iα knockdown. Interventions included siRNA‐mediated knockdown of REG Iα, overexpression of EDNRB, and pharmacological inhibition with the Ca2+ chelator BAPTA‐AM. Cell proliferation, apoptosis, migration, invasion, and epithelial‐mesenchymal transition (EMT) were assessed using Western blotting, RT‐qPCR, and Transwell assays. Results REG Iα was significantly upregulated in CRC tissues. Downregulation of REG Iα suppressed CRC cell proliferation, migration, and invasion while promoting apoptosis. Mechanistically, REG Iα silencing downregulated the expression of its target EDNRB and subsequently inhibited the Ca2+/CaMKII signaling pathway, triggering endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) accumulation to induce apoptosis. Importantly, overexpression of EDNRB rescued the malignant phenotypes suppressed by REG Iα knockdown, whereas BAPTA‐AM treatment abolished this rescue effect. The REG Iα/EDNRB axis was further demonstrated to drive the EMT process, and these findings were validated in vivo. Conclusions The REG Iα/EDNRB axis promotes the malignant progression of CRC by activating Ca2+‐dependent epithelial‐mesenchymal transition, suggesting that targeting this axis is a promising therapeutic strategy to inhibit CRC metastasis.

BACKGROUND:Conventional age <50 versus ≥50 years grouping may obscure colorectal cancer (CRC) burden patterns around the contemporary screening boundary. We examined whether adults aged 45-49 years occupy a threshold-adjacent position not captured by conventional grouping. METHODS:Using GBD 2023 data, we analyzed CRC incidence, deaths, and DALYs from 1990 to 2023 across four age groups (15-44, 45-49, 50-74, 75+ years). We assessed global and SDI-stratified trends, inequality, empirical lower-bound burden frontiers, and decomposition of burden change. Sensitivity analyses included conventional age regrouping, High versus Non-High SDI decomposition, split-period analyses, and adjacent 5-year age-group comparisons. RESULTS:Incidence rose most in adults aged 15-44 (+16.8%) and 45-49 years (+11.0%), with smaller increases in those aged 50-74 (+7.5%) and 75+ (+3.6%). Deaths and DALYs declined more clearly above age 50. In adults aged 45-49, incidence inequality remained positive but narrowed (CI: 0.304 to 0.253; relative SII: 1.693 to 1.412), while DALY inequality weakened (CI: 0.159 to 0.068). During 2010-2023, the residual rate-change component contributed positively to incidence in adults aged 45-49 globally (31.5%) but was slightly negative in those aged 50-74 (-2.6%). Post-2018 amplification in High-SDI populations was consistent with screening-related detection effects. CONCLUSIONS:Adults aged 45-49 occupy a context-dependent threshold-adjacent position in global CRC burden redistribution. These findings inform population-level surveillance and policy evaluation rather than individual-level clinical decision-making.

BackgroundTransanal total mesorectal excision (taTME) has become a promising surgical approach for anus-preserving surgery of mid-low rectal cancer (RC). This study aimed to compare the long-term oncological outcomes of taTME and laparoscopic total mesorectal excision (lapTME).MethodsOf 233 patients who were treated for mid-low RC from July 2017 to August 2020, 110 underwent taTME and 123 received lapTME. Propensity score matching (PSM) was performed to balance the baseline characteristics between the taTME and lapTME groups. After PSM, 61 patients were included in each group.ResultsPrior to PSM, the 5-year overall survival (OS) and disease-free survival (DFS) rates were comparable between the taTME and lapTME groups (72.7% vs. 69.1%, p = 0.617; 72% vs. 69%, p = 0.576, respectively). After PSM, there was no statistically significant difference in the 5-year OS and DFS rates between groups (64.2% vs. 64.4%, p = 0.936; 66.1% vs. 66.1%, p = 0.947, respectively).ConclusionAs compared to lapTME, taTME achieved comparable oncological safety for patients with mid-low RC.

Bevacizumab plus chemotherapy is the standard first-line therapy for metastatic colorectal cancer (mCRC). To date, no phase 3 trial has compared first-line oral multitargeted TKI versus bevacizumab plus chemotherapy in RAS/BRAF wild-type mCRC. The open-label, noninferiority, randomized, phase 3 trial (ANCHOR; NCT04854668; CTR20210940) evaluated first-line anlotinib versus bevacizumab plus oxaliplatin and capecitabine (CapeOX) in this setting. Patients were centrally randomized (1:1) to receive 4-8 cycles of CapeOX in combination with either anlotinib (12 mg once daily on days 1-14) or bevacizumab (7.5 mg/kg on day 1) every 3 weeks, followed by maintenance therapy with anlotinib or bevacizumab plus capecitabine until unacceptable toxicity or disease progression. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee in the intention-to-treat population. The hazard ratio (HR) for the noninferiority margin was 1.09. Between May 25, 2021, and August 30, 2023, 373 patients were assigned to the anlotinib group and 375 to the bevacizumab group. As of February 2, 2025, the median follow-up was 25.1 months (95% confidence interval [CI] 23.8-26.3). The median PFS was 11.0 months (95% CI 9.8-11.2) in the anlotinib group versus 11.0 months (9.7-11.2) in the bevacizumab group (stratified HR, 1.00; 95% CI 0.84-1.18; p = 0.87). The incidences of grade ≥3 treatment-related adverse events were 64.9% and 44.8%, respectively. Compared with bevacizumab plus CapeOX, anlotinib plus CapeOX showed similar antitumor activity but failed to reach the prespecified noninferiority margin for PFS and was associated with increased manageable toxicity.

Background For mid-to-low rectal cancer, although laparoscopic tumor resection (LapTME) has become a standard minimally invasive surgical approach, technical challenges remain in cases with complex anatomical structures. Transanal TME (TaTME) was developed to address these limitations, yet its widespread adoption has raised oncologic safety concerns in routine clinical practice. Most existing evidence comes from controlled trials using dual-team simultaneous approaches, while data on the common, resource-efficient single-team sequential approach remains insufficient. Methods This retrospective cohort study enrolled 256 consecutive patients with mid/low rectal adenocarcinoma undergoing curative TME at a tertiary center between 2018 and 2022. 2:1 propensity score matching balanced baseline covariates, generating 170 well-matched patients (108 in the one-team TaTME group, 62 in the LapTME group). We compared mid-term oncologic outcomes, perioperative safety, and pathologic margin status. Results After matching, median follow-up was 48 months. The TaTME group had longer operative time and a higher protective stoma rate, with comparable blood loss and postoperative complications. All patients achieved negative resection margins, while TaTME yielded a significantly more consistent distribution of distal margin length. At 3 years, no significant between-group differences were observed in local recurrence (3.7% vs 4.8%), distant metastasis (13.0% vs 14.5%), disease-free survival (83.3% vs 82.3%), or overall survival (88.9% vs 90.3%, all p > 0.05). Conclusions One-team TaTME achieved comparable mid-term oncologic outcomes to LapTME in routine practice, supporting its safety for experienced surgical teams. This real-world evidence facilitates the adoption of single-team TaTME in resource-limited settings.

Evidence for adjuvant chemotherapy (ACT) in very old gastric cancer patients is limited, and inadequate lymph node (LN) examination may affect staging and treatment selection. We assessed whether LN examination modifies the association between ACT and survival in older adults. From SEER (2010–2015), we identified patients aged ≥ 75 years who underwent resection for gastric cancer. LN examination was grouped as < 15 vs. ≥ 15. Overall survival (OS) was evaluated using Cox models. Cancer-specific death was analyzed with cumulative incidence functions and Fine–Gray regression. To mitigate treatment-selection bias, we used multivariable adjustment, propensity score matching (PSM), and stabilized inverse probability of treatment weighting (IPTW). Effect modification was tested using ACT×LN interaction terms; LN count was also explored continuously with restricted cubic splines. The cohort included 825 patients; 386 were retained after PSM. ACT–outcome estimates differed by LN examination. ACT was more favorably associated with outcomes among patients with ≥ 15 nodes examined, while estimates were weaker and less consistent when < 15 nodes were assessed. Interaction signals appeared in crude and some adjusted models but were attenuated, while remaining directionally consistent, in IPTW sensitivity analyses, suggesting susceptibility to residual confounding and modeling assumptions. Competing-risk analyses highlighted substantial non–cancer mortality. In a low-risk–exclusion cohort (N = 306), ACT remained favorably associated with outcomes, with less evidence of interaction. Among resected gastric cancer patients aged ≥ 75 years, the observed association between ACT and survival differed by LN examination extent, with more favorable estimates generally seen when ≥ 15 nodes are examined.

Metastasis and tumor relapses are the primary causes of mortality in breast cancer. Using an orthotopic xenograft mouse model implanted with bioluminescent-labeled wild-type and mdig knockout (KO) triple-negative breast cancer (TNBC) MDA-MB-231 cells, along with transcriptomics and chromatin immunoprecipitation and sequencing (ChIP-seq), we uncovered key molecular insights into mdig-mediated regulation of metastasis in TNBC. Although mdig KO cells formed smaller primary tumors, they exhibited increased lung and liver metastasis in vivo and greater invasive potential of circulating tumor cells in vitro. Restoring mdig expression in mdig KO cells reduced metastatic spread, particularly to the liver. Bulk RNA sequencing revealed up-regulation of metastasis-promoting genes in mdig KO cells, including SPOCK1, WNT5A, MAGEB2, TGFBI, SNAI2, VEGFA, and MAGED2. ChIP-seq analysis showed a global increase in histone H3 lysine 9 trimethylation (H3K9me3) and H3K36me3. Integrative RNA-sequencing and ChIP-seq analyses further demonstrated that genes associated with epithelial–mesenchymal transition and metastasis, such as KDM5C, IQSEC2, SMC1A, KLF8, RRAGB, FAM120C, and MAGED2, were highly enriched in genomic regions marked by dual H3K9me3 and H3K36me3. These regions appear to act as active enhancers through recruiting H3K4 monomethyl transferase SETD7 in mdig KO cells. Together, these findings establish mdig as a suppressor of TNBC metastasis and suggest that restoring mdig expression may help alleviate the metastatic burden in breast cancer by counteracting epigenetic changes that drive pro-metastatic gene expression.

INTRODUCTION:Intravenous LNP-mediated mRNA therapy holds promise for treating various diseases, yet its safety, particularly regarding adverse events, remains a critical concern. This review systematically evaluates the adverse effects associated with this therapeutic approach. METHODS:A comprehensive search of PubMed was conducted for clinical trials on intravenous LNP-mediated mRNA therapies. Data extraction focused on study design, participant demographics, and adverse events. Meta-analysis was performed to assess the incidence of treatment-emergent adverse events (TEAEs) and common manifestations. The risk of bias was assessed using the ROBINS-I tool. RESULTS:A total of six phase 1/2 clinical trials on intravenous LNP-mediated mRNA therapies were included, with sample sizes ranging from 6 to 38 participants. The pooled incidence of TEAEs was 92.2% (95% CI: 77.7%-99.4%). Sensitivity analysis indicated that excluding one study with a single smaller dose reduced heterogeneity to 6.8%. The incidence of severe TEAEs was 9.2% (95% CI: 0%-38.1%) and showed substantial heterogeneity (I2 = 89.87%), which was likely influenced by factors such as higher doses, multiple administrations, and patient-specific conditions like comorbidities. CONCLUSION:While low-dose, single-dose intravenous LNP-mediated mRNA therapies generally have a manageable safety profile, higher doses or repeated administrations may increase the risk of severe adverse events. PROTOCOL REGISTRATION:www.crd.york.ac.uk/prospero identifier is CRD42025643741.

Medulloblastoma (MB), particularly Group_3 (G3-MB), remains the most aggressive subgroup due to strong stemness and therapeutic resistance. Through genome-wide DNA methylation and transcriptomic analysis of human MB samples, we identify enhancer hypomethylation as a key feature sustaining G3-MB stemness and tumor progression. Notably, hypomethylation of the Otx2 super-enhancer (SE) is a prognostic marker and potential therapeutic target for G3-MB patients. We demonstrate that disrupting Otx2 SE activity effectively reduces tumor growth in vivo, highlighting its critical role in G3-MB maintenance. TET3, recruited by OTX2, demethylates the Otx2 SE, promoting chromatin opening and sustaining tumor proliferation and stemness. To translate these findings into therapy, we develop a liposomal nanoparticle (LNP)-based delivery system for siTET3 or a cytosine-based inhibitor of TET3, achieving significant tumor-suppressive effect in a patient-derived orthotopic xenograft model of G3-MB. Our study provides the targeted approach for Otx2-driven G3-MB and introduces LNP-based epigenetic therapy as a promising low-toxicity strategy.

BackgroundThe tumor microenvironment (TME) significantly impacts the progression and prognosis of medulloblastoma (MB). This study aimed to develop a TME-associated risk score(TMErisk) model using RNA sequencing data to predict patient outcomes and elucidate biological mechanisms.MethodsRNA sequencing data from 322 Tiantan and 763 GSE85217 MB samples were analyzed. Key gene modules related to immune and stromal components were identified using Weighted Gene Co-expression Network Analysis (WGCNA). Significant genes were screened using LASSO-COX and COX regression models. Single-cell RNA sequencing (scRNA-seq), single-cell ATAC sequencing (scATAC-seq), and spatial RNA analyses validated the findings.ResultsDifferential expression analysis identified 731 upregulated and 15 downregulated genes in high vs. low immune score MB patients, and 686 upregulated and 43 downregulated genes in high vs. low stromal score patients. Eight key genes (CEBPB, OLFML2B, GGTA1, GZMA, TCIM, OLFML3, NAT1, and CD1C) were included in the TMErisk model, which demonstrated strong prognostic power. High TMErisk scores correlated with poorer survival, distinct immune cell infiltration patterns, and lower tumor cell stemness. Single-cell analyses revealed the expression dynamics of TMErisk genes across cell types, including macrophages, T cells, and NK cells, and identified key regulatory transcription factors. Spatial transcriptomics showed significant clustering of TMErisk genes in tumor regions, highlighting spatial heterogeneity and the formation of immune hubs.ConclusionsThe TMErisk model enhances our understanding of the MB tumor microenvironment, serving as a robust prognostic tool and suggesting new avenues for targeted therapy.

Inflammatory bowel disease is a risk factor for brain dysfunction; however, the underlying mechanisms remain largely unknown. In this study, we aimed to explore the potential molecular mechanisms through which intestinal inflammation affects brain function and to verify these mechanisms. Mice were treated with multiple cycles of 1% w/v dextran sulfate sodium (DSS) in drinking water to establish a chronic colitis model. Behavioral tests were conducted using the open field test (OFT), tail suspension test (TST), forced swimming test (FST), and Morris water maze test (MWM). Brain metabolomics, transcriptomics, and proteomics analyses were performed, and key target proteins were verified using qPCR and immunofluorescence. Four cycles of DSS administration induced colitis, anxiety, depression, and spatial memory impairment. The integrated multi-omics characterization of colitis revealed decreased brain chenodeoxycholic acid (CDCA) levels as well as reduced stearoyl-CoA desaturase (Scd1) gene and protein expression. Transplantation of the colitis microbiome resulted in anxiety, depression, impaired spatial memory, reduced CDCA content, decreased Scd1 gene and protein expression, and lower concentrations of monounsaturated fatty acids (MUFAs), palmitoleate (C16:1), and oleate (C18:1) in the brain. In addition, CDCA supplementation improved DSS-induced colitis, alleviated depression and spatial memory impairment, and increased Scd1 gene and protein expression as well as MUFA levels in the brain. The gut microbiome induced by colitis contributes to neurological dysfunction, possibly through the CDCA-Scd1 signaling axis. CDCA supplementation alleviates colitis and depressive behavior, likely by increasing Scd1 expression in the brain.

Humic acid (HA), a complex organic substance naturally present in soil, peat, and coal, is traditionally referred to as the extract of "Wujinshi" () in Chinese medicine. It is renowned for its potent anti-inflammatory, analgesic, and blood circulation-promoting properties. However, its mechanisms and delivery methods require further exploration. We developed BiHANs, a novel nanoparticle combining bismuth and HA, which exhibits excellent biocompatibility and anti-inflammatory effects in vitro. Orally administered BiHANs accumulate at inflammatory sites in the colon of DSS-induced IBD mice, as confirmed by CT imaging, and prolong intestinal retention. They significantly alleviate acute and chronic intestinal damage by suppressing inflammatory responses, modulating gut microbiota, and targeting macrophage mitochondria to inhibit NF-κB-driven cytokine production. BiHANs also maintain mitochondrial homeostasis and exert antioxidative effects. Furthermore, their performance in CT imaging highlights potential as a theranostic agent. This study demonstrates BiHANs as a promising platform for targeted IBD therapy and diagnosis, combining anti-inflammatory efficacy with imaging capabilities.

Background: Mounting evidence exhibits circRNAs as critical regulators in the progression of many tumors. The regulatory function and potential mechanism by which circ_0008126 in gastric cancer (GC) is unknown. Methods: To validate and analyze the expression levels and clinical values of circ_0008126 in GC patients, the biological phenotypes of circ_0008126 in GC were investigated in vitro and in vivo. The roles and effects of circ_0008126 on miR-502-5p, EIF4A3, and APC in GC cells were explored using rescue experiment, RNA stability assay, RNA pull-down, dual-luciferase reporter, RNA immunoprecipitation (RIP), RNA FISH, immunofluorescence (IF), and TOP/Flash and FOP/Flash assays. Results: Circ_0008126 expression levels were prominently down-regulated in GC tissues and cells. Importantly, low expression of circ_0008126 was relevant to the more lymphatic metastasis, advanced TNM stage, and poor survival period in patients with GC. Functionally, circ_0008126 inhibited GC cell proliferative activity, metastatic ability, and epithelial-mesenchymal transition (EMT) in vitro and vivo. Mechanistically, we verified that EIF4A3 can mediate the formation of circ_0008126, and circ_0008126 could competitively bind miR-502-5p and alleviate its role and effect on APC, thus inactivating the β-catenin pathway in GC. Additionally, circ_0008126 was determined to increase the stability of APC mRNA by interacting with cytoplasmic EIF4A3 protein and then enhancing the APC expression. Conclusions: These data demonstrate that EIF4A3-mediated circ_0008126 could regulate the APC expression and inactivate the β-catenin pathway partly by binding to miR-502-5p and EIF4A3, thus inhibiting the tumorigenesis and development of GC.

Background:Surgery is the cornerstone of treatment for colorectal cancer (CRC), and postoperative prognosis is a hot topic in CRC research. Although body mass index (BMI) is closely related to the occurrence and development of CRC, its impact on prognosis remains controversial. The purpose of this study is to explore the impact of different BMI levels on the postoperative prognosis of CRC. Methods:Two hundred and four patients who underwent primary radical CRC surgery in the Department of Gastrointestinal Surgery of The First Affiliated Hospital of Chongqing Medical University from January 2019 to June 2019 were retrospectively collected. According to BMI, they were classified into low/normal weight (BMI <24 kg/m2), overweight (24 kg/m2 ≤ BMI <28 kg/m2), and obese (BMI ≥28 kg/m2) groups. The clinicopathological features, tumor antigens, blood tests, serum biochemical indices, peripheral blood immune cell flow cytometry, recurrence/progression-free survival (RPFS), and overall survival (OS) were compared between the two groups. Results:Overweight BMI emerged as an independent protective factor, markedly lowering the risk of CRC recurrence or progression [hazard ratio (HR) =0.367; 95% confidence interval (CI): 0.175-0.769] and cancer-related mortality (HR =0.273; 95% CI: 0.105-0.714). Overweight patients consequently exhibited significantly better RPFS (P=0.02) and OS (P=0.004). Peripheral CD8+ T cell (P=0.04) and CD3+CD4-CD8- T cell counts (P=0.03) differed significantly across BMI groups, with both subsets markedly reduced in the peripheral blood of overweight patients. Alanine aminotransferase (ALT; P<0.001), γ-glutamyl transferase (GGT; P=0.004), bicarbonate (HCO3 -; P=0.004), and glucose (P<0.001) also differed among BMI groups. Postoperative course-complications and length of stay-did not differ significantly among BMI groups (P=0.70). Conclusions:Overweight patients exhibited significantly better prognosis, possibly attributable to an activated immune status and adequate nutritional reserves, suggesting that CRC patients might benefit from appropriate perioperative weight gain.

LBA3502 Background: Anti-VEGF antibodies combined with chemotherapy remain first-line treatment for unresectable metastatic colorectal cancer (mCRC), but no randomised trials have evaluated oral VEGFR-TKI plus chemotherapy in this setting. Methods: In this Chinese multicenter, randomised, non-inferiority, phase 3 trial, treatment-naïve RAS/BRAF wild-type mCRC patients with MDT-assessed unresectable metastases were 1:1 randomised to receive anlotinib (12mg, QD, days 1-14) or bevacizumab (7.5mg/kg, IV, day 1), both combined with oxaliplatin (130mg/m², IV, day 1) and capecitabine (anlotinib group:850mg/m2, bevacizumab group 1000mg/m², BID, days 1-14) in 3-week cycles. After 4-8 induction cycles, maintenance therapy with anlotinib or bevacizumab plus capecitabine continued until progression/unacceptable toxicity. Stratification factors were tumor location (right/left) and prior adjuvant chemotherapy (yes/no). Primary endpoint was IRC-assessed PFS (non-inferiority margin HR≤1.09); secondary endpoints included investigator-assessed PFS, ORR, DCR, DoR, OS, liver metastases resection rate, and quality of life. With one-sided α=0.025 and 81.2% of power, 524 PFS events were required. Results: Between May 25th, 2021 to August 30th, 2023, 748 patients were randomly assigned and included in the intention-to-treat population, with 373 in anlotinib group and 375 in bevacizumab group. Patients had a median age of 59.0 years (IQR, 53.0-67.0) and 227 (30.35%) of all 748 patients were female. The median follow-up was 25.10 months (95% CI, 23.82-26.25). The median IRC-assessed PFS in anlotinib and bevacizumab group were 11.04 months (95% CI, 9.82-11.17) and 11.04 months (9.69-11.17), respectively, with HR 1.00 (0.84-1.18). Serious adverse events occurred in 143 (38.34%) of 373 patients in anlotinib group, and in 129 of 375 (34.40%) patients in bevacizumab group. Conclusions: In unresectable RAS/BRAF wild-type mCRC patients, anlotinib plus CapeOX showed comparable PFS time and safety compared with bevacizumab plus CapeOX. The results provide a new treatment option for unresectable RAS/BRAF wild-type mCRC patients. Clinical trial information: NCT04854668 . Anlotinib plus CapeOX (n=373) Bevacizumab plus CapeOX (n=375) HR (95% CI) ORR (95% CI), % 61.93% (56.79-66.88) 62.13% (57.01-67.06) DCR (95% CI), % 92.76% (89.64-95.18) 93.07% (90.01-95.42) Median DoR (95% CI), months 9.66 (8.31-9.99) 9.69 (8.48-11.01) 1.04 (0.84-1.27) Resection rate of liver metastases, % 3.75% 2.93% Grade ≥3 TEAE, n (%) 276 (73.99) 222 (59.20) TEAE leading to treatment discontinuation, n (%) 30 (8.04) 34 (9.07) TEAE leading to death, n (%) 16 (4.29) 17 (4.53)

To analyze the relationship between Helicobacter pylori (HP) infection degree and miR-155 and miR-543 expression levels in gastric cancer (GC). GC patients were retrospectively enrolled (n = 405), with their baseline data, 2-year follow-up records, and prognosis collected and analyzed. miR-155 and miR-543 expression levels in GC tissues were first predicted online and then determined in GC patient tissues using RT-qPCR. The correlations between miR-155 and miR-543 expression patterns and the U value of HP infection were analyzed through Spearman coefficient. A multivariate Cox regression model was established to analyze the risk factors for 2-year postoperative death of HP-positive GC patients. Kaplan-Meier curves were plotted to analyze the impact of miR-155 and miR-543 on the 2-year prognosis of HP-positive GC patients. miR-155 and miR-543 were upregulated in GC tissues and cells, with significantly higher expression levels in HP-positive compared to HP-negative patients. miR-155 and miR-543 expression changes were correlated with the HP infection degree. There were significant differences in miR-155 and miR-543 expression patterns across tumor diameter, TNM staging, and lymph node metastasis degree. Upregulated miR-155 and miR-543, TNM stage III, and lymph node metastasis were independent risk factors for 2-year postoperative death in HP-positive GC patients. Upregulated miR-155 and miR-543 increased the 2-year postoperative death rate. miR-155 and miR-543 were upregulated in HP-positive GC patients, and their expression changes were correlated with HP infection degree. High miR-155 and miR-543 expression increased the risk of 2-year postoperative death in HP-positive GC patients.