T-cell lymphomas (TCLs) are heterogeneous malignancies with limited treatment options and poor outcomes. The efficacy of traditional T-cell therapies, including chimeric antigen receptor (CAR) T cells, is often constrained by immunosuppressive factors and the tumor microenvironment. On the other hand, although direct Granzyme B (GrB) administration can effectively induce tumor cell apoptosis, it lacks universal tumor targeting and efficient cellular entry mechanisms. To address these limitations, we developed a novel nanoparticle-based therapy for the precise targeting of TCL tumor cells and the delivery of GrB. We fused nanobody (Nb) targeting CD30 and CD5 with GrB and coupled them to human ferritin (h-HFn) using the Gv/Sd system, creating a novel therapeutic nanoparticle named BiCD30/5-GF, which specifically targets CD30 and CD5 receptors on TCL tumor cells. The Nb-GrB conjugation enhances tumor targeting, while a Gv/Sd linker coupled to h-HFn further improves cellular transport and targeting. Additionally, the multimerization of GrB enhances its effectiveness. These nanoparticles demonstrated superior binding affinity and cytotoxicity in vitro compared to conventional treatments. In vivo studies on tumor-bearing mice showed significant tumor suppression and prolonged survival following treatment with BiCD30/5-GF nanoparticles. We also extended similar nanoparticle strategies for gastric cancer therapy, targeting FGFR4-expressing tumor cells. Our findings highlight the potential of engineered nanoparticles as effective and targeted therapeutic agents across various tumor types, offering promising prospects for clinical translation in cancer treatment.

BACKGROUND:Clonal hematopoiesis of indeterminate potential (CHIP) has been shown to be associated with the occurrence of solid tumors, but its relationship with colorectal cancer still needs to be studied. METHODS:We conducted a prospective matched case-control study using data from the UK Biobank, including 5,310 incident colorectal cancer cases and 26,550 controls matched for age, sex, and body mass index. RESULTS:Analysis of the UK Biobank data revealed that the presence of CHIP was associated with an increased risk of colorectal cancer. The odds ratio (OR) for colorectal cancer in the presence of CHIP was 1.20 (P = 0.006). This association remained significant even after excluding participants with a family history of bowel cancer (multivariate OR, 1.19; P = 0.007). Subgroup analyses demonstrated that CHIP independently increased the risk of colorectal cancer in females (multivariate OR, 1.25; P = 0.018) and in individuals older than 60 years (multivariate OR, 1.17; P = 0.046). Gene-specific analyses revealed that mutations in TET2 and ATM were particularly significant in relation to colorectal cancer risk, with an OR of 1.62 (P = 0.002) for TET2 and 2.98 (P < 0.001) for ATM. CONCLUSIONS:Our findings indicate that CHIP is associated with an increased risk of colorectal cancer, particularly in individuals more than 60 years of age or in females. IMPACT:Screening for CHIP in the population may improve the early detection and diagnosis rates of colorectal cancer.

Gastric cancer ranks among the most prevalent malignancies globally, characterized by limited treatment efficacy and high recurrence rates. Effective management of this disease requires a comprehensive understanding of its underlying pathogenic mechanisms. Galectins have emerged as promising targets in gastric cancer therapy, with Galectin-9 (LGALS9) receiving considerable attention in recent years. However, Galectin-9B (LGALS9B) remains relatively under-explored in gastric cancer research. Our study investigates the role of LGALS9B in gastric cancer progression, demonstrating that its over-expression enhances cellular proliferation, migration, and invasion, while its knockdown inhibits these processes both in vitro and in vivo. We further elucidate that LGALS9B competes with the E3 ligase HERC5 for binding to eukaryotic translation elongation factor 1 delta (EEF1D), thereby preventing its protein degradation. This interaction results in the enrichment of EEF1D, which activates the PI3K/AKT signaling pathway and ultimately promotes gastric cancer progression. These findings highlight the regulatory role of LGALS9B in the pathogenesis of gastric cancer, offering valuable insights into potential novel therapeutic strategies for managing this challenging disease.

Background: Stomach adenocarcinoma (STAD) with microsatellite instability (MSI) have better prognosis compared with nonMSI. This study aims to elucidate the distinctions in the tumor microenvironment (TME) of MSI and explore its potential mechanisms in STAD. Methods: We analyzed TME differences between MSI and non-MSI using integrated single-cell RNA sequencing (N = 26) and bulk RNA sequencing (N = 237). Differentially expressed genes unveiled key pathways and hub genes, and TNFSF9 expression was validated through immunohistochemistry (IHC) quantitative polymerase chain reaction (qPCR) and Western blot analysis (WB). Results: The results demonstrated a significant association between MSI and improved prognosis (p < 0.05), along with a higher tumor mutation burden (p < 0.05). Our study revealed increased abundance of antigen-presenting cells (APCs) in MSI, including M1 cells (40.1% vs. 27.9%) and activated dendritic cells (22.1% vs. 10.5%). Signaling pathway and cell communication analyses indicated the enrichment of cytokine-related pathways in MSI. The findings further revealed an increased expression of TNFSF9 by tumor epithelial cells in MSI. Correlation analysis revealed a positive association between TNFSF9 expression and increased APC abundance. IHC, qPCR, and WB validation revealed increased TNFSF9 expression in MSI tumor epithelial cells. Conclusions: These results offer new insights into the TME in MSI, emphasizing the significant role of TNFSF9 in mediating MSI status, enhancing immunotherapy efficacy, and improving patient survival in STAD.

Background: The current study proposed a novel subtype, Human papillomavirus (HPV)-infected colorectal cancer (CRC), to understand the impact of HPV on CRC. Methods: We assessed the prevalence and clinical implications of HPV in CRC by integrating a single cohort in Guangdong Provincial People's Hospital and public datasets. Differential gene, pathway enrichment, and immune infiltration analysis were conducted to explore the patterns in HPV-infected CRC. Quantitative polymerase chain reaction, cell proliferation, scratch, and flow cytometry assays were employed to validate the impact of HPV on CRC. Results: The study revealed a high prevalence of HPV infection in CRC, with infection rates ranging from 10% to 31%. There was also a significant increase in tumor proliferation in HPV-infected CRC. The study showed increased immune cell infiltration, including T cells, gamma delta T cells, cytotoxic cells, and plasmacytoid dendritic cells in HPV-infected CRC ( P < 0.05). Furthermore, our findings confirmed that HPV infection promoted M1 polarization. Our results demonstrated that low ISM2 expression was associated with a less advanced clinical stage ( P < 0.001) and better survival outcomes ( P 1 / 4 0.039). Low ISM2 expression correlated with a strong tumor immune response, potentially contributing to the improved survival observed in HPV-infected CRC. Conclusions: These findings provided a novel subtype of HPV-infected CRC. The subtype with a better prognosis showed a "hot " tumor immune microenvironment that may be responsive to immunotherapy. (c) 2024 The Authors. Published by Elsevier Masson SAS on behalf of Institut Pasteur. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Importance: Gastric cancer is often diagnosed at an advanced stage and at order age, identification of high-risk population is needed for detection of early-stage gastric cancer. Objective: To examine whether clonal hematopoiesis of indeterminate potential (CHIP) is a risk factor of gastric cancer. Design: This cohort study used data from the UK Biobank collected from baseline (2006–2010) to the end of follow-up in March 2024. Setting: Data on age, sex, race, alcohol consumption, smoking status and type 2 diabetes were collected at baseline interview. Previous and diagnosed cancer or diseases were collected from self-reported and in-hospital records. Participants: Participants with no previous cancer or hematologic disorders were selected. Participants with gastric cancer cases were aged 60.7 (S.D. 6.62), 71.8 % male; controls were aged 56.1 (S.D. 8.11), 47.4 % male. Exposures: Whole-exome sequencing was performed on blood samples collected at baseline. A CHIP status was identified based on the mutations on 43 CHIP-related genes. Main outcomes and measures: Odds ratio (OR) of CHIP with gastric cancer risk was estimated using multivariable logistic regression models. Participants were grouped based on age and CHIP status to examine if there are differences in the cumulative incidence of gastric cancer. Results: Among 402,253 participants, 1,070 incident gastric cancer cases were identified (mean age, 60.7 ± 6.62 years). The prevalence of CHIP at baseline was associated with an increased risk of gastric cancer (cases: 6.54 % vs. controls 5.14 %; OR without adjustment, 1.29; 95 % CI, 1.004 to 1.63). The stratified OR (95 % CI) of individuals aged ≥ 57 was 1.33 (1.02 to 1.72) for overall CHIP, whereas the OR for younger individuals was 0.79 (0.37 to 1.44). CHIP involving DNMT3A (OR, 1.81; 95 % CI, 1.05 to 2.88; P = 0.0193) and ASXL1 (OR, 2.43; 95 % CI, 0.95 to 4.99; P = 0.032) was associated with an increased risk of gastric cancer. These positive associations remained significantly in sensitivity analyses adjusted by known risk factors. Compared to younger individuals and non-CHIP carriers, older participants with CHIP exhibited a significantly higher cumulative incidence of gastric cancer (P < 0.0001). Conclusions and relevance: CHIP is associated with gastric cancer in the elderly and contributes to the positive association between DNM3A and ASXL1 mutations and risk of gastric cancer.

N 6-Methyladenosine (m6A) 6 A) modification and its regulators play critical roles in human cancers, but their functions and regulatory mechanisms in adenocarcinoma of the esophagogastric junction (AEG) remain unclear. Here, we identified that IGF2BP3 is the most significantly up-regulated m6A 6 A regulator in AEG tumors versus paired normal adjacent tissues from the expression profile of m6A 6 A regulators in a large cohort of AEG patients. Silencing IGF2BP3 inhibits AEG progression in vitro and in vivo. . By profiling transcriptome-wide targets of IGF2BP3 and the m6A 6 A methylome in AEG, we found that IGF2BP3-mediated stabilization and enhanced expression of m6A-modified 6 A-modified targets, including targets of the cell cycle pathway, such as CDC25A, , CDK4, , and E2F1, , are critical for AEG progression. Mechanistically, the increased m6A 6 A modification of CDC25A accelerates the G1-S transition. Clinically, up-regulated IGF2BP3, METTL3, and CDC25A show a strong positive correlation in TCGA pan-cancer, including AEG. In conclusion, our study highlights the role of post-transcriptional regulation in modulating AEG tumor progression and elucidates the functional importance of the m6A/IGF2BP3/CDC25A 6 A/IGF2BP3/CDC25A axis in AEG cells.

Osteophyte formation, a key indicator of osteoarthritis (OA) severity, remains poorly understood in its relation to gut microbiota and metabolites in knee osteoarthritis (KOA). We conducted 16S rDNA sequencing and untargeted metabolomics on fecal and serum samples from 20 healthy volunteers, 80 KOA patients in Guangdong, and 100 in Inner Mongolia, respectively. Through bioinformatics analysis, we identified 3 genera and 5 serum metabolites associated with KOA osteophyte formation. Blautia abundance negatively correlated with meat, cheese, and bean consumption. The 5 serum metabolites negatively correlated with dairy, beef, cheese, sugar, and salt intake, yet positively with age and oil consumption. Higher Blautia levels in the gut may contribute to KOA osteophyte formation, with serum metabolites LTB4 and PGD2 potentially serving as biomarkers. KOA patients in Inner Mongolia exhibited lower Blautia levels and reduced expression of 5 serum metabolites, possibly due to cheese consumption habits, resulting in less osteophyte formation.

Background Colorectal cancer (CRC) is a prevalent malignant tumor characterized by high global incidence and mortality rates. Furthermore, it is imperative to comprehend the molecular mechanisms underlying its development and to identify effective prognostic markers. These efforts are crucial for pinpointing potential therapeutic targets and enhancing patient survival rates. Therefore, We develop a novel prognostic model aimed at providing new theoretical support for clinical prognosis evaluation and treatment. Methods We downloaded data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Subsequently, we performed single-cell analysis and developed a prognostic model associated with colorectal cancer. Results We divided the scRNA-seq dataset (GSE221575) into 19 cell clusters and classified these clusters into 11 distinct cell types using marker genes. Using univariate Cox regression and LASSO (Least Absolute Shrinkage and Selection Operator) analyses, we developed a prognostic model consisting of 9 genes. Based on our 9-gene model, we divided patients into high-risk and low-risk groups using the median risk score. The high-risk group demonstrated significant positive correlations with M0 macrophages, CD8 + T cells, and M2 macrophages. The enrichment analyses indicate significant enrichment of immune-related pathways in the high-risk group, including HEDGEHOG_SIGNALING, Wnt signaling pathway, and cell adhesion molecules. Drug sensitivity analysis revealed that the low-risk group was sensitive to 5 chemotherapeutic drugs, while the high-risk group was sensitive to only 1. Additionally, we developed a highly reliable nomogram for clinical application. This suggests that the risk score derived from our modeling analysis is highly effective for stratifying colorectal cancer samples. Conclusions This study comprehensively applied bioinformatics methods to construct a risk score model. The model showed good predictive performance, offering potential guidance for individualized treatment of colorectal cancer patients. Furthermore, it may provide valuable insights into the disease's pathogenesis and identify potential therapeutic targets for further research.

The success of immunotherapy for cancer treatment is limited by the presence of an immunosuppressive tumor microenvironment (TME); Therefore, identifying novel targets to that can reverse this immunosuppressive TME and enhance immunotherapy efficacy is essential. In this study, enrichment analysis based on publicly available single-cell and bulk RNA sequencing data from gastric cancer patients are conducted, and found that tumor-intrinsic interferon (IFN) plays a central role in TME regulation. The results shows that KDM3A over-expression suppresses the tumor-intrinsic IFN response and inhibits KDM3A, either genomically or pharmacologically, which effectively promotes IFN responses by activating endogenous retroviruses (ERVs). KDM3A ablation reconfigures the dsRNA-MAVS-IFN axis by modulating H3K4me2, enhancing the infiltration and function of CD8 T cells, and simultaneously reducing the presence of regulatory T cells, resulting in a reshaped TME in vivo. In addition, combining anti-PD1 therapy with KDM3A inhibition effectively inhibited tumor growth. In conclusions, this study highlights KDM3A as a potential target for TME remodeling and the enhancement of antitumor immunity in gastric cancer through the regulation of the ERV-MAVS-IFN axis.

BackgroundRecent research indicates a positive correlation between DEP structural domain-containing 1B (DEPDC1B) and the cell cycle in various tumors. However, the role of DEPDC1B in the infiltration of the tumor immune microenvironment (TIME) remains unexplored.MethodsWe analyzed the differential expression and prognostic significance of DEPDC1B in colon adenocarcinoma (COAD) using the R package "limma" and the Gene Expression Profiling Interactive Analysis (GEPIA) website. Gene set enrichment analysis (GSEA) was employed to investigate the functions and interactions of DEPDC1B expression in COAD. Cell Counting Kit-8 (CCK-8) assays and colony formation assays were utilized to assess the proliferative function of DEPDC1B. Correlations between DEPDC1B expression and tumor-infiltrating immune cells, immune checkpoints, tumor mutational burden (TMB), and microsatellite instability (MSI) status were examined using Spearman correlation analysis and CIBERSORT.ResultsDEPDC1B was highly expressed in COAD. Elevated DEPDC1B expression was associated with lower epithelial-to-mesenchymal transition (EMT) and TNM stages, leading to a favorable prognosis. DEPDC1B mRNA was prominently expressed in COAD cell lines. CCK-8 and colony formation assays demonstrated that DEPDC1B inhibited the proliferation of COAD cells. Analysis using the CIBERSORT database and Spearman correlation revealed that DEPDC1B correlated with four types of tumor-infiltrating immune cells. Furthermore, high DEPDC1B expression was linked to the expression of PD-L1, CTLA4, SIGLEC15, PD-L2, TMB, and MSI-H. High DEPDC1B expression also indicated responsiveness to anti-PD-L1 immunotherapy.ConclusionsDEPDC1B inhibits the proliferation of COAD cells and positively regulates the cell cycle, showing a positive correlation with CCNB1 and PBK expression. DEPDC1B expression in COAD is associated with tumor-infiltrating immune cells, immune checkpoints, TMB, and MSI-H in the tumor immune microenvironment. This suggests that DEPDC1B may serve as a novel prognostic marker and a potential target for immunotherapy in COAD.

Although oxaliplatin (OXA) is widely used in the frontline treatment of colorectal cancer (CRC), CRC recurrence is commonly observed due to OXA resistance. OXA resistance is associated with a number of factors, including abnormal regulation of pyroptosis. It is therefore important to elucidate the abnormal regulatory mechanism underlying pyroptosis. Here, we identified that the circular RNA circPDIA3 played an important role in chemoresistance in CRC. CircPDIA3 could induce chemoresistance in CRC by inhibiting pyroptosis both in vitro and in vivo. Mechanistically, RIP, RNA pull-down and co-IP assays revealed that circPDIA3 directly bonded to the GSDME-C domain, subsequently enhanced the autoinhibitory effect of the GSDME-C domain through blocking the GSDME-C domain palmitoylation by ZDHHC3 and ZDHHC17, thereby restraining pyroptosis. Additionally, it was found that the circPDIA3/miR-449a/XBP1 positive feedback loop increased the expression of circPDIA3 to induce chemoresistance. Furthermore, our clinical data and patient-derived tumor xenograft (PDX) models supported the positive association of circPDIA3 with development of chemoresistance in CRC patients. Taken together, our findings demonstrated that circPDIA3 could promote chemoresistance by amplifying the autoinhibitory effect of the GSDME-C domain through inhibition of the GSDME-C domain palmitoylation in CRC. This study provides novel insights into the mechanism of circRNA in regulating pyroptosis and providing a potential therapeutic target for reversing chemoresistance of CRC.

Along with social development and lifestyle changes, the number of overweight and obese patients worldwide is rising annually. Obesity is a chronic metabolic disease with complex etiology. Dipeptidyl peptidase IV (DPP-IV) is a novel adipokine with significantly elevated expression in the visceral fat of obese patients. DPP-IV is a molecule that regulates metabolic homeostasis and inflammatory processes. Through its enzymatic activity, it plays a significant part in achieving hypoglycemic and weight loss effects through various pathways. DPP-IV and DPP-IV inhibitors also have pleiotropic effects in modulating obesity-related diseases by reducing obesity-related inflammation, ameliorating inflammatory bowel disease (IBD), improving hepatic steatosis and lowering cardiovascular risk, and even decreasing the risk of novel coronavirus disease-19 (COVID-19). This paper reviews the mechanisms of action based on DPP-IV targets in obesity and metabolic homeostasis, as well as their active role in the treatment of chronic diseases associated with obesity.

Background: Accumulating evidence have highlighted the essential roles of HOX genes in embryonic development and carcinogenesis. As a member of the HOX gene family, the abnormal expression of HOXC8 gene is associated with the progression and metastasis of various tumors. However, potential roles of HOXC8 in colorectal cancer (CRC) prognosis and tumor microenvironment (TME) remodeling remain unclear. Methods: We conducted an integrated analysis of clinical and molecular characteristics, relevant oncogenic and immune regulation roles and drug sensitivity features of HOXC8 in CRC. Results: HOXC8 expression was markedly high expressed in CRC samples compared to normal samples, and the upregulated expression of HOXC8 was associated with poor prognosis. High HOXC8 expression was significantly associated with invasion-related pathways especially epithelial-mesenchymal transition (EMT). In vitro experiments showed significantly up-regulated HOXC8 expression in some CRC cell lines and its promoting effect on EMT and cell proliferation. TME categorization through transcriptomic analysis of CRC patients with high HOXC8 expression identified two different TME subtypes known as immune-enriched with fibrotic subtype and immune-depleted subtype. Patients with immune-enriched, fibrotic subtype exhibited significantly longer progression-free survival (PFS), upregulated PD-L1 and CTLA4 expression and higher TMB than those with the immune-depleted subtype. Conclusions: HOXC8 overexpression was associated with poor prognosis and specific TME subtypes in CRC. This study provided valuable resource for further exploring the potential mechanisms and therapeutic targets of HOX genes in CRC.

Objective:To compare the curative effect of transverse colon resection and extended colon resection in the treatment of transverse colon cancer, and to find a suitable surgical method to provide reference for clinical treatment.Methods:The clinicopathological data of patients with transverse colon cancer who received surgical treatment in the gastrointestinal surgery department of Guangdong Provincial People's Hospital from January 2006 to December 2019 were collected. Analyze the differences in surgical survival and clinical indicators between the two groups.Results:A total of 366 patients were included, including 58 cases of transverse colon resection and 308 cases of extended colon resection. There was no significant difference in 5-year overall survival rate and 5-year disease-free survival rate between the transverse colon resection group and the extended colon resection group (all P＞0.05).There was no significant difference in the 5-year overall survival rate between the transverse colon resection group and the extended colon resection group in patients with TNM stage I, II and III (all P＞0.05).The amount of intraoperative bleeding in the transverse colon resection group was less than that in the extended colon resection group [(55.0±29.0) mL, (96.9±28.3) mL], and the number of lymph nodes cleared in the transverse colon resection group was less than that in the extended colon resection group [(19.5±8.4), (23.1±11.4)], which were statistically significant (all P＜0.05).The results of univariate analysis showed that postoperative T stage, postoperative N stage, vascular cancer thrombus invasion, postoperative chemotherapy, surgical approach, tumor gross classification, and tumor differentiation were risk factors affecting patient prognosis (all P＜0.05).The inclusion of single factor risk factors in multivariate analysis showed that postoperative T stage, postoperative N stage, vascular tumor thrombus invasion, postoperative chemotherapy, surgical approach, tumor gross classification, and tumor differentiation were all independent risk factors affecting patient survival and prognosis (all P＜0.05).Conclusion:Transverse colectomy has the same long-term prognosis as extended colectomy in the treatment of patients with transverse colon cancer. Transverse colectomy does not increase the risk of postoperative complications. Transverse colectomy can be safely used in patients with transverse colon cancer.

The use of mRNA vaccines to treat colon cancer (CC) remains largely unexplored. The aim of this study is to identify CC antigens that may potentially be used for the development of anti‐CC mRNA vaccines and to select suitable patients for vaccination. Immune subtypes are identified by consensus clustering analysis, and the visualization of the CC immune landscape is performed by graph‐learning‐based dimensionality reduction. Plot cell trajectory and the WGCNA are applied to resolve the heterogeneity of the population suitable for vaccination. Four tumor antigens, COQ2, BGN, CASP6, and FAP, which are related to prognosis and infiltration of antigen‐presenting cells, are identified in CC. CC patients are divided into four immune subtypes characterized by differential molecular, cellular, pathological, and clinical features. Group B has the characteristics of immunologically “cold” tumors, and the immunosuppressive phenotype has worse survival than other groups. Moreover, different immune subtype tumors differed in the expression of immune checkpoints and immunogenic cell death modulators. Last, immune cell components in individual patients are revealed by the immune landscape. COQ2, BGN, CASP6, and FAP are potential antigens for use in a CC‐mRNA vaccine and suitable for patients in Group B.

Oxaliplatin is commonly used in chemotherapeutic regimens for colorectal cancer (CRC) after surgical resection. However, acquired chemoresistance seriously affects the curative effect in CRC patients, and the mechanism is still unclear. Here, a circular RNA, circATG4B is identified, which plays an important role in oxaliplatin resistance in CRC. circATG4B expression is found to be increased in exosomes secreted by oxaliplatin-resistant CRC cells. In addition, the results suggest that circATG4B induces oxaliplatin resistance by promoting autophagy. Further in vivo and in vitro studies indicate that the effect of circATG4B is attributed to its potential to encode a novel protein, circATG4B-222aa. Next, circATG4B-222aa is found to function as a decoy to competitively interact with TMED10 and prevent TMED10 from binding to ATG4B, which leads to increased autophagy followed by induction of chemoresistance. Therefore, this study reveals that exosomal circATG4B participates in the decreased chemosensitivity of CRC cells, providing a new rationale for a potential therapeutic target for oxaliplatin resistance in CRC.

Objective:To investigate the clinical efficacy of proximal gastrectomy and total gastrectomy in the treatment of Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective cohort study was conducted. The clinicopathological data of 170 patients with Siewert type Ⅱ and Ⅲ AEG who were admitted to Guangdong Provincial People′s Hospital from January 2010 to December 2018 were collected. There were 125 males and 45 females, aged from 30 to 85 years, with a median age of 64 years. Of the 170 patients, 82 cases undergoing proximal gastrectomy were allocated into the proximal gastrectomy group and 88 cases undergoing total gastrectomy were allocated into the total gastrectomy group. Observation indica-tors: (1) surgical and postoperative situations; (2) follow-up and survival; (3) analysis of prognostic factors. Follow-up was conducted using telephone interview and outpatient examination to detect survival of patients up to December 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measure-ment data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Kaplan-Meier method was used to draw survival curves, and Log-Rank test was used for survival analysis. COX proportional hazard model was used for univariate and multivariate analyses. Variables with P<0.1 in univariate analysis were included for multivariate analysis. Results:(1) Surgical and postoperative situations. Cases with surgical approach as transthoracic or thoraco-abdominal approach, transabdominal approach, the operation time, cases with volume of intra-operative blood loss ≤100 mL or >100 mL, cases with length of proximal margin ≤1.5 cm or >1.5 cm, cases with radical surgery outcome as R 0, R 1, R 2, the number of lymph nodes harvest, cases with anastomotic leakage, cases with anastomotic stricture, cases with incision infection, cases with pleural infection or effusion, cases with abdominal infection or ascites were 61, 21, (211±18)minutes, 46, 36, 44, 38, 73, 6, 3, 15(9,22), 5, 2, 2, 4, 2 in the proximal gastrectomy group, respec-tively. The above indicators were 12, 76, (263±15)minutes, 27, 61, 45, 43, 82, 4, 2, 23(18,32), 4, 1, 3, 1, 4 in the total gastrectomy group, respectively. There were significant differences in the surgical approach, operation time, volume of intraoperative blood loss and the number of lymph nodes harvest between the two groups ( χ2=63.94, t=-25.50, χ2=11.19, Z=-5.62, P<0.05). There was no significant difference in the length of proximal margin or radical surgery outcome between the two groups ( χ2=0.11, Z=-0.95, P>0.05) and there was no significant difference in the anastomotic leakage, anastomotic stricture, incision infection, pleural infection or effusion, abdominal infection or ascites between the two groups ( P>0.05). (2) Follow-up and survival. All the 170 patients were followed up for 89(64,106)months. Of the 170 patients, the 5-year overall survival rates were 43.8% and 35.5% of the Siewert type Ⅱ and Ⅲ AEG patients, respectively, showing no significant difference between them ( χ2=0.87, P>0.05). Of the patients with Siewert type Ⅱ AEG, the 5-year overall survival rates were 41.7% and 54.3% in the patients with proximal gastrectomy and the total gastrectomy, respectively, showing no significant difference between them ( χ2=1.05, P>0.05). Of the patients with Siewert type Ⅲ AEG, the 5-year overall survival rates were 31.3% and 37.5% in the patients with proximal gastrectomy and the total gastrectomy, respectively, showing no significant difference between them ( χ2=0.33, P>0.05). The 5-year overall survival rates were 39.0% and 44.2% in the proximal gastrectomy group and the total gastrectomy group, respectively, showing no significant difference between the two groups ( χ2=0.63, P>0.05). Of the patients in TNM stage Ⅰ, stage Ⅱ, stage Ⅲ, the 5-year overall survival rates were 65.3%, 36.3%, 27.1% in the proximal gastrectomy group, versus 83.3%, 48.0%, 39.7% in the total gastrectomy group, showing no signifi-cant difference between the two groups ( χ2=0.02, 1.50, 1.21, P>0.05). (3) Analysis of prognostic factors. Results of univariate analysis showed that pathological N staging, degree of tumor differen-tiation and radical surgery outcome were related factors influencing prognosis of AEG patients ( hazard ratio=1.71, 1.70, 2.85, 95% confidence interval as 1.16-2.60, 1.15-2.50, 1.58-5.14, P<0.05). Results of multivariate analysis showed that pathological N staging and radical surgery outcome were independent factors influencing prognosis of AEG patients ( hazard ratio=1.55, 2.18, 95% confidence interval as 1.05-2.31, 1.18-4.02, P<0.05). Conclusions:There is no significant difference in the prognosis of Siewert type Ⅱ and Ⅲ AEG patients undergoing proximal gastrectomy or total gastrectomy. Proximal gastrectomy can be used for the treatment of advanced Siewert type Ⅱ and Ⅲ AEG.

Background: We aimed to investigate the association between optimal examined lymph node (ELNs) and overall survival to determine the optimal cutoff point. Methods: Cox models and locally weighted scatterplot smoothing were used to fit hazard ratios and explore an optimal cutoff point based on the Chow test. Results: Overall survival increased significantly with the corresponding increase in the number of ELNs after adjusting for covariates. In Chow's test, the optimal cutoff point for node-negative colon cancer was 15, which was validated in both cohorts after controlling for confounders (Surveillance, Epidemiology, and End Results database: hazard ratio: 0.701, p < 0.001; single-center: HR: 0.563; p = 0.031). Conclusions: We conservatively suggest that the optimal number of ELNs for prognostic stratification is 15 in node-negative colon cancer.

Background To evaluate the prognostic impact of the advanced lung cancer index (ALI) in patients with the adenocarcinoma of esophagogastric junction (AEG) after radical resection. Methods The data of patients with AEG after radical resection at Guangdong Provincial People’s Hospital from January 2008 to December 2018 were retrieved. The cutoff value of ALI was determined and the prognostic impact of clinicopathological factors and ALI were analyzed. A nomogram based on the independent prognostic factors for overall survival was then built. Results A total of 147 patients were eligible and based on a cutoff of ALI 43.1, 90 (61.2%) and 57 (38.8%) patients were classified in a low- (ALI༜43.1) and high-ALI (ALI༞43.1) group. Multivariate Cox proportional hazard analysis showed that low-ALI was associated with poor overall survival (OS) (p༜0.001, HR 2.541, 95%CI 1.408-4.410) and disease-free survival (DFS) (p=0.021, HR 1.789, 95%CI 1.020-2.674). In subgroup analysis, low-ALI was independent predictor for OS (p=0.001, HR 2.628, 95%CI 1.467-4.707) in stage III/IVA AEG patients. A nomogram for OS estimation was constructed and the C-index was 0.699 (95%CI 0.636-0.762) and the calibration plots showed satisfactory consistency between actual observation and nomogram-predicted OS probabilities. Further, satisfactory predictive accuracy for 1-, 2-, and 3-year OS rates with an area under the curve of 0.736, 0.712 and 0.697, respectively, was observed. Conclusions ALI was an independent prognostic factor for AEG patients after radical resection, and demonstrated promising ability for risk stratification of AEG, especially in advanced-stage disease.