Akkermansia muciniphila-derived pentadecanoic acid enhances oxaliplatin sensitivity in gastric cancer by modulating glycolysis.

Accumulating evidence has proved the close association between alterations in gut microbiota and resistance to chemotherapeutic drugs. However, the potential roles of gut microbiota in regulating oxaliplatin sensitivity in gastric cancer (GC) have not been investigated before. We first found that antibiotic treatment diminished the therapeutic efficacy of oxaliplatin in a GC mouse model. Importantly, this effect could be transmitted to germ-free mice via fecal microbiota transplantation, indicating a potential role of gut microbiota modulation in oxaliplatin efficacy. Further, metagenomics data showed that Akkermansia muciniphila (A. muciniphila) ranked first among the bacterial species with decreased relative abundances after antibiotic treatment. Metabolically active A. muciniphila promotes oxaliplatin efficacy. As shown by metabolomics analysis, the metabolic pattern of gut microbiota was disrupted with significantly downregulated levels of pentadecanoic acid (PEA), and the use of PEA significantly promoted oxaliplatin efficacy. Mechanistically, FUBP1 positively regulated aerobic glycolysis of GC cells to hinder the therapeutic efficacy of oxaliplatin. A. muciniphila-derived PEA functioned as an inhibitory factor of glycolysis by directly antagonizing the activity of FUBP1, which potentiated GC responses to oxaliplatin. Our research suggested a key role for intestinal A. muciniphila and its metabolite PEA in promoting oxaliplatin efficacy, thus providing a new perspective for probiotic and prebiotic intervention in GC patients during chemotherapy.

Clinicopathologic factors correlated with lymph node metastasis in gastric cancer: a retrospective cohort study involving 5606 patients.

BACKGROUND: The identification of risk factors associated with lymph node metastasis (LNM) in gastric cancer will establish a crucial foundation for the implementation of endoscopic operation and multidisciplinary treatment programs. METHODS: A total of 5606 patients with gastric cancer with comprehensive clinicopathologic data were enrolled through systematic searching and rigorous screening. Of the 5606 patients, 1438 were diagnosed with early gastric cancer (EGC), which would be used for further analysis. Subsequently, univariate and multivariate logistic regression analyses were performed to identify the risk factors. RESULTS: The rates of LNM in T1a, T1b, T2, T3, T4a, and T4b stage gastric cancer were 7.0%, 19.4%, 48.4%, 77.1%, 83.8%, and 89.6%, respectively. Female (odds ratio [OR], 1.559; P = .032), lower tumor location (OR, 1.773; P = .023), tumor size of >2 cm (OR, 2.007; P < .001), mixed (OR, 2.371; P = .001) and undifferentiated histologic types (OR, 2.952; P < .001), T1b stage (OR, 2.041; P < .001), presence of ulceration (OR, 1.758; P = .027), and lymphovascular invasion (OR, 5.722; P < .001) were identified as independent risk factors for LNM in EGC. A nomogram was constructed using appropriate predictors to preoperatively predict the risk of LNM in patients with EGC. CONCLUSION: This study identified the clinicopathologic factors associated with LNM in patients with EGC and developed a prediction model, thereby facilitating the integration of diverse treatment modalities in managing patients with EGC.

Risk factors associated with lymph node metastasis in early-stage distal gastric cancer.

OBJECTS: This study was designed to explore the risk factors of lymph node metastasis (LNM) in distal gastric cancer with early stage, and to provide reference for the choice of treatment protocols. METHODS: In this retrospective observational study, 824 early distal gastric cancer (EDGC) cases who treated at our unit from 2010 to 2020 were selected as research objects. Subsequently, univariate and multivariate logistic regression analyses were conducted to investigate the associations between LNM and clinicopathological features. RESULTS: Of these 824 EDGC cases, 140 (17.0%) developed LNM, including 72 N1 stage and 68 N2-3 stage LNM. Multivariate logistic regression analysis identified the tumor diameter ≥1.75 cm (odds ratio (OR) = 2.361, p < 0.001), tumor location (OR = 1.552, p = 0.046), histological classification (p = 0.004), tumor infiltration depth (OR = 2.154, p = 0.001), and vascular infiltration (OR = 4.354, p < 0.001) as independent predictors for LNM. Logistic regression analyses based on 756 N0-1 LNM cases identified the smoking history (OR = 0.507, p = 0.043), tumor diameter ≥1.75 cm (OR = 2.265, p = 0.010), tumor location (OR = 1.834, p = 0.036), histological classification (p = 0.018), tumor infiltration depth (OR = 1.939, p = 0.034), and vascular infiltration (OR = 3.225, p < 0.001) as independent predictors for N1 LNM. Moreover, preoperative hypoalbuminemia (OR = 7.087, p = 0.015), significant preoperative weight loss (OR = 2.724, p = 0.023), tumor diameter ≥1.75 cm (OR = 5.484, p = 0.001), multiple tumors (OR = 9.986, p = 0.038), histological classification (p = 0.029), and vascular infiltration (OR = 33.704, p < 0.001) were proved to be associated with LNM for T1a tumors. CONCLUSIONS: The tumor diameter, location and infiltration depth, histological classification, and vascular infiltration were expected to be used as predictors of LNM in EDGC, and preoperative hypoalbuminemia, significant weight loss, tumor diameter and number, histological classification, and vascular infiltration were associated with LNM for T1a tumors.

Total versus proximal gastrectomy for proximal gastric cancer after neoadjuvant chemotherapy: a multicenter retrospective propensity score-matched cohort study.

BACKGROUND: This study aimed to analyze and compare the short-term and long-term outcomes of proximal gastrectomy (PG) and total gastrectomy (TG) in patients with locally advanced proximal gastric cancer (GC) following neoadjuvant chemotherapy (NACT). METHOD: A multicenter retrospective cohort study and propensity score matching (PSM) were employed. The authors examined 367 patients with proximal GC who received NACT followed by PG ( n =164) or TG ( n =203) at two Chinese medical institutions between December 2009 and December 2022. Clinical and pathological parameters, postoperative complications, and 5-year overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups. The dissection status and metastasis rate of each lymph node station were assessed. RESULTS: After PSM, 80 patients were enrolled in both TG and PG group, and baseline characteristics were comparable between the groups (all P >0.05). The TG group had a higher total number of lymph nodes retrieved ( P <0.001) and longer operative time ( P =0.007) compared to the PG group. The incidence of Clavien-Dindo grade II or higher postoperative complications was similar between the TG group (21.3%, 17/80) and the PG group (17.5%, 14/80) ( P =0.689). The 5-year OS rates were 68.4 for the PG group and 66.0% for the TG group ( P =0.881), while the 5-year RFS rates were 64.8 and 61.9%, respectively ( P =0.571), with no statistically significant differences. Metastasis rates at lymph node stations #4d, #5, #6, and #12a were notably low in the TG group, with values of 2.74, 0.67, 1.33, and 1.74%, respectively. CONCLUSION: For proximal GC patients following NACT, PG maintains comparable curative potential and oncological efficacy to TG, making it a safe option.

Predictors and outcomes of recurrent retroperitoneal liposarcoma: new insights into its recurrence patterns.

BACKGROUND: The clinical profiles of recurrent retroperitoneal liposarcoma (RLS) need to be explored. The recurrence patterns of RLS are controversial and ambiguous. METHODS: A total of 138 patients with recurrent RLS were finally recruited in the study. The analysis of overall survival (OS) and recurrence-free survival (RFS) was performed by Kaplan‒Meier analysis. To identify independent prognostic factors, all significant variables on univariate Cox regression analysis (P ≤ 0.05) were subjected to multivariate Cox regression analysis. The corresponding nomogram model was further built to predict the survival status of patients. RESULTS: Among patients, the 1-, 3-, and 5-year OS rates were 70.7%, 35.9% and 30.9%, respectively. The 1-, 3- and 5-year RFS rates of the 55 patients who underwent R0 resection were 76.1%, 50.8% and 34.4%, respectively. The multivariate analysis revealed that resection method, tumor size, status of pathological differentiation, pathological subtypes and recurrence pattern were independent risk factors for OS or RFS. Patients with distant recurrence (DR) pattern usually had multifocal tumors (90.5% vs. 74.7%, P < 0.05); they were prone to experience changes of pathological differentiation (69.9% vs. 33.3%, P < 0.05) and had a better prognosis than those with local recurrence (LR) pattern. R0 resection and combined organ resection favored the survival of patients with DR pattern in some cases. CONCLUSIONS: Patients with DR pattern had better prognosis, and they may benefit more from aggressive combined resection than those with LR pattern. Classifying the recurrence patterns of RLS provides guidance for individualized clinical management of recurrent RLS.

Early Outcomes of Different Reconstruction Procedures in Radical Distal Gastrectomy: A Retrospective Propensity Score Matching Study.

OBJECTIVE: To evaluate the short-term effects of Billroth I (B-I), Billroth Ⅱ (B-Ⅱ), Billroth Ⅱ+Braun (B-B), and Roux-en-Y (R-Y) reconstruction procedures in radical distal gastrectomy using propensity score matching (PSM). MATERIALS AND METHODS: The clinical data of 1994 patients who underwent radical distal gastrectomy in the past 10 years were retrospectively analyzed. Subsequently, PSM analyses were performed 3 times on the 4 reconstruction procedures, and the matching capacity was set to 0.01. Data regarding control variables and outcome indicators obtained using PSM were compared and analyzed. RESULTS: Compared with the other reconstruction procedures, patients in the B-I group had shorter operation time ( P =0.002), fewer abdominal drainage tubes ( P <0.001), and a lower risk of postoperative gastroparesis ( P =0.001) and gastrointestinal bleeding ( P =0.034), but tended to experience a longer postoperative indwelling time of bladder catheter ( P <0.001), gastrointestinal decompression ( P <0.001), fasting ( P =0.001), and hospital stays ( P =0.005). The B-B group tended to have fewer applications of the abdominal drainage tube ( P =0.014), a lower risk of postoperative gastrointestinal fistula ( P =0.040), shorter postoperative time of gastrointestinal decompression ( P =0.043), fasting ( P <0.001), and a shorter hospital stay ( P <0.001) than the R-Y group. Furthermore, the B-B group had a shorter postoperative time for gastrointestinal decompression ( P =0.014) and fasting ( P <0.001) than the B-Ⅱ group. CONCLUSION: Billroth I reconstruction has the advantages of simple operation, short operative time, and few early complications, but tends to result in a long recovery time during postoperative hospitalization. The B-B operation is associated with faster postoperative recovery than the R-Y or B-Ⅱ operation.

Predictors and outcomes of recurrent retroperitoneal liposarcoma with multiple tumors.

Background: Retroperitoneal liposarcoma (RLS) is a rare but severe disease. Repeated postoperative recurrence with multiple tumors is a therapeutic dilemma. The clinical outcomes and survival predictors of recurrent RLS with multiple tumors remain to be explored. Methods: Patients with recurrent RLS were retrospectively analyzed. Univariate and multivariate analysis was performed to find independent prognostic factors that were correlated with Overall survival (OS) or progression-free survival (PFS). Factors significant in univariate analysis were further included into multivariate Cox proportional hazards regression model. The nomogram model was built to predict the survival status of patients. Variables that were significant in multivariable analysis were added to the internally validated nomogram models. The analysis of OS and PFS was performed by Kaplan-Meier analysis and log-rank test. Results: A total of 113 recurrent RLS patients with multiple tumors were enrolled in the study. The 1-, 3-, and 5-years OS (PFS) rates were 70.7% (76.1%), 35.9% (76.1%), and 30.9% (76.1%), respectively. Univariate and multivariate analyses showed that number of surgeries, resection methods, tumor size, status of pathological differentiation, pathological subtypes, and recurrence patterns were important prognostic factors for OS or PFS (each p < 0.05). Nomogram models were established to efficiently predict the prognostic status of patients. Patients with the local recurrence (LR) pattern had a poor prognosis and would derive no survival benefit from combined organ resection and R0/R1 resection (each p < 0.05). Conclusion: RLS patients recurrence with multiple tumors had a poor prognosis. Those patients should be followed up more frequently after surgery. The strategies of aggressive resection may not improve the survival of patients with LR pattern in the retroperitoneum. Prognostic factors in the efficient nomogram models should be considered in the individualized clinical management of recurrent RLS with multiple tumors.

Critical Signaling Transduction Pathways and Intestinal Barrier: Implications for Pathophysiology and Therapeutics.

The intestinal barrier is a sum of the functions and structures consisting of the intestinal mucosal epithelium, mucus, intestinal flora, secretory immunoglobulins, and digestive juices. It is the first-line defense mechanism that resists nonspecific infections with powerful functions that include physical, endocrine, and immune defenses. Health and physiological homeostasis are greatly dependent on the sturdiness of the intestinal barrier shield, whose dysfunction can contribute to the progression of numerous types of intestinal diseases. Disorders of internal homeostasis may also induce barrier impairment and form vicious cycles during the response to diseases. Therefore, the identification of the underlying mechanisms involved in intestinal barrier function and the development of effective drugs targeting its damage have become popular research topics. Evidence has shown that multiple signaling pathways and corresponding critical molecules are extensively involved in the regulation of the barrier pathophysiological state. Ectopic expression or activation of signaling pathways plays an essential role in the process of shield destruction. Although some drugs, such as molecular or signaling inhibitors, are currently used for the treatment of intestinal diseases, their efficacy cannot meet current medical requirements. In this review, we summarize the current achievements in research on the relationships between the intestinal barrier and signaling pathways. The limitations and future perspectives are also discussed to provide new horizons for targeted therapies for restoring intestinal barrier function that have translational potential.

Predictive factors and a novel nomogram for recurrence of primary retroperitoneal liposarcoma: Comprehensive analysis of 128 cases.

Since primary retroperitoneal liposarcoma (PRPLS) is rare in the clinic, related clinical studies are lacking. The present study was designed to investigate the predictive factors of short-term (≤1 year) recurrence (STR) and construct a novel nomogram of local recurrence-free survival (LRFS) for surgically resected PRPLS. A total of 128 PRPLS cases who underwent radical surgery were retrospectively analyzed. Based on the interval from the operation to tumor recurrence, the predictors of STR were screened using univariate and multivariate logistic regression analyses. Cox proportional hazard regression models were applied to identify the predictors of LRFS. Furthermore, the independent predictors acquired from multivariate analyses were used to construct a nomogram. Multivariate logistic regression analysis revealed that age ≥55 years [odds ratio (OR)=5.607, P=0.010], operative time ≥260 min (OR=9.716, P=0.005) and tumor necrosis (OR=3.781, P=0.037) were independent risk factors of STR for PRPLS. In the Cox regression analysis, clinical symptoms [hazard ratio (HR)=1.746, P=0.017], resection method (OR=0.370, P=0.021) and de-differentiated histological subtype (HR=1.975, P=0.048) were identified as independent predictors of LRFS. Subsequently, the independent predictors acquired from multivariate analyses were used to construct a nomogram for LRFS. Age, operative time, tumor necrosis, clinical symptoms, resection method and histological subtype were related to recurrence for surgically resected PRPLS and a novel nomogram was constructed based on the above predictors.

LncRNA CCAT2 promotes malignant progression of metastatic gastric cancer through regulating CD44 alternative splicing.

OBJECTIVE: Gastric cancer (GC) is one of the most malignant tumors worldwide. Thus, it is necessary to explore the underlying mechanisms of GC progression and develop novel therapeutic regimens. Long non-coding RNAs (lncRNAs) have been demonstrated to be abnormally expressed and regulate the malignant behaviors of cancer cells. Our previous research demonstrated that lncRNA colon cancer-associated transcript 2 (CCAT2) has potential value for GC diagnosis and discrimination. However, the functional mechanisms of lncRNA CCAT2 in GC development remain to be explored. METHODS: GC and normal adjacent tissues were collected to detect the expression of lncRNA CCAT2, ESRP1 and CD44 in clinical specimens and their clinical significance for GC patients. Cell counting kit-8, wound healing and transwell assays were conducted to investigate the malignant behaviors in vitro. The generation of nude mouse xenografts by subcutaneous, intraperitoneal and tail vein injection was performed to examine GC growth and metastasis in vivo. Co-immunoprecipitation, RNA-binding protein pull-down assay and fluorescence in situ hybridization were performed to reveal the binding relationships between ESRP1 and CD44. RESULTS: In the present study, lncRNA CCAT2 was overexpressed in GC tissues compared to adjacent normal tissues and correlated with short survival time of patients. lncRNA CCAT2 promoted the proliferation, migration and invasion of GC cells. Its overexpression modulates alternative splicing of Cluster of differentiation 44 (CD44) variants and facilitates the conversion from the standard form to variable CD44 isoform 6 (CD44v6). Mechanistically, lncRNA CCAT2 upregulated CD44v6 expression by binding to epithelial splicing regulatory protein 1 (ESRP1), which subsequently mediates CD44 alternative splicing. The oncogenic role of the lncRNA CCAT2/ESRP1/CD44 axis in the promotion of malignant behaviors was verified by both in vivo and in vitro experiments. CONCLUSIONS: Our findings identified a novel mechanism by which lncRNA CCAT2, as a type of protein-binding RNA, regulates alternative splicing of CD44 and promotes GC progression. This axis may become an effective target for clinical diagnosis and treatment.

The association between the body roundness index and the risk of colorectal cancer: a cross-sectional study.

BACKGROUND: Colorectal cancer (CRC), has a link between obesity, especially visceral fat. The body roundness index (BRI) can more accurately assess body fat and visceral fat levels. It is, however, unknown whether BRI is associated with CRC risk. METHODS: 53,766 participants were enrolled from the National Health and Nutrition Examination Survey (NHANES). Analysing the corelation between BRI and CRC risk was performed using logistic regression. Stratified analyses revealed the association based on the population type. Receiver operating characteristic curve (ROC) was performed for predicting CRC risk using different anthropometric indices. RESULTS: The risk of CRC mounting apparently with elevated BRI for participants with CRC compared to normal participants (P-trend < 0.001). The association persisted even after adjusting for all covariates (P-trend = 0.017). In stratified analyses, CRC risk increased with increasing BRI, especially among those who were inactive (OR (95% CI): Q3 3.761 (2.139, 6.610), P < 0.05, Q4 5.972 (3.347, 8.470), P < 0.01), overweight (OR (95% CI): Q3 2.573 (1.012, 7.431), P < 0.05, Q4 3.318 (1.221, 9.020), P < 0.05) or obese (OR (95% CI): Q3 3.889 (1.829, 8.266), P < 0.001, Q4 4.920 (2.349, 10.308), P < 0.001). ROC curve showed that BRI had a better ability in forecasting the risk of CRC than other anthropometric indices such as body weight etc. (all P < 0.05). CONCLUSIONS: CRC risk and BRI have a positive and significant relationship, particularly in inactive participants with BMI ≥ 25 kg/m2. It is hoped that these results will raise awareness of the importance of reducing visceral fat deposition.

Correlation Analysis Between Demographic, Surgical, and Pathological Characteristics with Local Recurrence-Free Survival for Surgical Resected Retroperitoneal Liposarcoma.

BACKGROUND: As the leading cause of mortality for retroperitoneal liposarcoma (RPLS) cases, postoperative recurrence has complicated and unclear risk factors. This study was conducted to explore the correlations between demographic, surgical, and pathological characteristics with local recurrence-free survival (LRFS) for surgical resected RPLS. METHODS: RPLS cases that underwent radical operation were considered to be included in this analysis. LRFS rates were estimated based on the Kaplan-Meier method and were compared between groups by the log-rank test. Cox proportional hazard regression models were constructed to identified the predictors of LRFS. Subsequently, the independent predictors acquired from multivariate analyses were used to construct a nomogram. RESULTS: 348 RPLS cases who underwent radical operation were included. Of the 348 cases, 333 had tumor recurrence or with a follow-up period ≥5 years. Thus, 296 (88.9%) of the 333 cases had recurrent disease, and the median LRFS duration of 296 recurrence cases was 17.0 (95% confidence interval (CI) 13.2-20.8) months. Multivariate analysis identified the preoperative neutrophil/lymphocyte ratio (NLR), surgical frequency, operative time, tumor shape, histological subtype, and tumor necrosis as independent predictors of LRFS. Based on above independent predictors, a nomogram was constructed to predict the 1-, 3-, and 5-year LRFS of surgical resected RPLS. CONCLUSION: Elevated preoperative NLR, ≥2nd time surgical frequency, extended operation time, irregular tumor shape, no well-differentiated histological subtype, and tumor necrosis could be used as predictors of LRFS for surgical resected RPLS.

Inhibition of androgen receptor enhanced the anticancer effects of everolimus through targeting glucose transporter 12.

Everolimus was designed as a mammalian target of rapamycin (mTOR) inhibitor. It has been proven as a targeted drug for gastric cancer (GC) therapy. However, long-term treatment with everolimus may cause severe side effects for recipients. Decreasing the dosage and attenuating the associated risks are feasible to promote clinical translation of everolimus. This study aimed to identify the underlying mechanisms of responses to everolimus and develop novel regimens for GC treatment. Our findings proved that there was a significant dose-dependent relationship of everolimus-induced GC cell apoptosis and glycolysis inhibition. Then, we found that a member of glucose transporter (GLUT12) family, GLUT12, was actively upregulated to counteract the anticancer effects of everolimus. GLUT12 might be overexpressed in GC. High expression of GLUT12 might be correlated with tumor progression and short survival time of GC patients. Bioinformatic analysis suggested that GLUT12 might be involved in regulating cancer development and metabolism. The experiments proved that GLUT12 significantly promoted GC growth, glycolysis and impaired the anticancer effects of everolimus. Androgen receptor (AR) is a classical oncogenic factor in many types of cancer. Everolimus elevated GLUT12 expression in an AR-dependent manner. Inhibition of AR activity abrogated the promotive effects on GLUT12 expression. Both in-vitro and in-vivo experiments demonstrated that GLUT12 knockdown augmented anticancer effects of everolimus. Enzalutamide, an AR inhibitor, or AR knockdown was comparable to GLUT12 suppression. This study identified the role of the AR/GLUT12 pathway in the development of poor responses to everolimus. Interference with AR/GLUT12 pathway may serve as a promising approach to promoting the translational application of everolimus in GC therapy.

Melatonin supplementation protects against traumatic colon injury by regulating SERPINA3N protein expression.

Traumatic colon injury (TCI) is a typical injury with high mortality. Prolongation of the intervention time window is a potentially useful approach to improving the outcomes of TCI casualties. This study aimed to identify the pathological mechanisms of TCI and to develop effective strategies to extend the survival time. A semicircular incision was made to prepare a TCI model using C57BL/6 mice. An overview of microbiota dysregulation was achieved by metagenome sequencing. Protein expression reprogramming in the intestinal epithelium was investigated using proteomics profiling. The mice that were subjected to TCI died within a short period of time when not treated. Gut symbiosis showed abrupt turbulence, and specific pathogenic bacteria rapidly proliferated. The protein expression in the intestinal epithelium was also reprogrammed. Among the differentially expressed proteins, SERPINA3N was overexpressed after TCI modeling. Deletion of Serpina3n prolonged the posttraumatic survival time of mice with TCI by improving gut homeostasis in vivo. To promote the translational application of this research, the effects of melatonin (MLT), an oral inhibitor of the SERPINA3N protein, were further investigated. MLT effectively downregulated SERPINA3N expression and mitigated TCI-induced death by suppressing the NF-κB signaling pathway. Our findings prove that preventive administration of MLT serves as an effective regimen to prolong the posttraumatic survival time by restoring gut homeostasis perturbed by TCI. It may become a novel strategy for improving the prognosis of patients suffering from TCI.

Comparison of short-term efficacy between totally laparoscopic gastrectomy and laparoscopic assisted gastrectomy for elderly patients with gastric cancer.

BACKGROUND: Totally laparoscopic gastrectomy (TLG) entails both gastrectomy and gastrointestinal reconstruction under laparoscopy. Compared with laparoscopic assisted gastrectomy (LAG), TLG has been demonstrated in many studies to require a smaller surgical incision, result in a faster postoperative recovery and less pain and have comparable long-term efficacy, which has been a research hotspot in recent years. Whether TLG is equally safe and feasible for elderly patients remains unclear. AIM: To compare the short-term efficacy of and quality of life (QOL) associated with TLG and LAG in elderly gastric cancer (GC) patients. METHODS: The clinicopathological data of 462 elderly patients aged ≥ 70 years who underwent LAG or TLG (including distal gastrectomy and total gastrectomy) between January 2017 and January 2022 at the Department of General Surgery, First Medical Center, Chinese PLA General Hospital were retrospectively collected. A total of 232 patients were in the LAG group, and 230 patients were in the TLG group. Basic patient information, clinicopathological characteristics, operation information and QOL data were collected to compare efficacy. RESULTS: Compared with those in the LAG group, intraoperative blood loss in the TLG group was significantly lower (P < 0.001), and the time to first flatus and postoperative hospitalization time were significantly shorter (both P < 0.001). The overall incidence of postoperative complications in the TLG group was significantly lower than that in the LAG group (P = 0.01). Binary logistic regression results indicated that LAG and an operation time > 220 min were independent risk factors for postoperative complications in elderly patients with GC (P < 0.05). In terms of QOL, no statistically significant differences in various preoperative indicators were found between the LAG group and the LTG group (P > 0.05). Compared with the laparoscopic-assisted total gastrectomy group, patients who received totally laparoscopic total gastrectomy had lower nausea and vomiting scores and higher satisfaction with their body image (P < 0.05). Patients who underwent laparoscopic-assisted distal gastrectomy were more satisfied with their body image than patients in the totally laparoscopic distal gastrectomy group (P < 0.05). CONCLUSION: TLG is safe and feasible for elderly patients with GC and has outstanding advantages such as reducing intracorporeal blood loss, promoting postoperative recovery and improving QOL.

circDNMT1 Promotes Malignant Progression of Gastric Cancer Through Targeting miR-576-3p/Hypoxia Inducible Factor-1 Alpha Axis.

Background: Circular RNAs (circRNAs) regulate multiple malignant behaviors of various types of cancer. The role of circDNMT1, a newly identified circRNA, remains unknown in gastric cancer (GC). This study aimed to elucidate the underlying mechanisms of circDNMT1 in regulating GC progression. Methods: microRNA (miRNA) and circRNA expression was detected by quantitative real-time PCR. Western blotting was performed to measure hypoxia inducible factor-1 alpha (HIF-1α) protein expression. Sanger sequencing, gel electrophoresis and fluorescence in situ hybridization were performed to identify the presence of circDNMT1. The clinicopathological features and overall survival of patients were analyzed based on circDNMT1 expression. The proliferation, migration and invasion of GC cells were determined by cell counting kit-8, 5-ethynyl-2'-deoxyuridine, wound healing and transwell assays. Glycolysis of GC cells was detected based on the levels of glucose uptake, the lactate acid, ATP and pyruvic acid production and the extracellular acidification and oxygen consumption rates. The binding sites between miR-576-3p and circDNMT1 or HIF-1α were predicted by online bioinformatic tools and were validated using RNA pull-down and luciferase reporter assays. Xenograft models were established to determine the effects of the circDNMT1/miR-576-3p/HIF-1α axis on GC growth and metastasis in vivo. Results: circDNMT1 was successfully identified and shown to be overexpressed in GC tissues and cell lines. The expression levels of circDNMT1 were correlated with pathological T stage, pathological TNM stage and shorter survival time of GC patients. circDNMT1 knockdown inhibited the proliferation, migration, invasion and glycolysis of GC cells. circDNMT1 functioned as an oncogenic factor by sponging miR-576-3p. HIF-1α was negatively regulated by miR-576-3p via binding its mRNA 3' untranslated region. circDNMT1 promoted malignant behaviors and metabolic reprogramming of GC by targeting the miR-576-3p/HIF-1α axis both in vitro and in vivo. Conclusion: These findings demonstrated that circDNMT1 knockdown inhibited GC proliferation, migration, invasion and glycolysis through sponging miR-576-3p/HIF-1α axis. circDNMT1 may be a novel target for GC treatment.