Preoperative contributing factors and the remission of diabetes after metabolic surgery: the mediating role of preoperative triglyceride.

BACKGROUND AND OBJECTIVE: Limited understanding exists regarding the factors affecting the prognosis of surgical treatment for type 2 diabetes mellitus (T2DM), particularly in Chinese patients. In this study, we examined a cohort of early and intermediate obese T2DM patients to explore the potential impact of preoperative lipid metabolism in metabolic surgery on the postoperative remission of T2DM. METHODS: Participants with T2DM and obesity underwent metabolic surgery. Clinical data, including baseline body mass index, percentage of excess weight loss, and preoperative biochemical indicators, were collected and analyzed. A multidisciplinary team conducted patient follow-up. Remission was defined as sub-diabetic hyperglycemia (HbA1c < 48 mmol/mol, fasting glucose 100-125 mg/dl) without pharmacological intervention for at least 12 months. RESULTS: Over a median follow-up of 27 months, 96 T2DM patients with metabolic surgery were studied, with no laparotomies required. Among these patients, 61 (63.5%) achieved complete remission, and 85 (88.5%) experienced remission. In multivariable analysis models, preoperative fasting blood glucose (FBG) significantly correlated with all postoperative outcomes. Furthermore, mediation analysis indicated that preoperative triglycerides (TG) mediated 26.31% of the association between preoperative FBG and postoperative remission. Both preoperative FBG and TG were negatively associated with the postoperative remission of T2DM. CONCLUSION: In summary, our findings suggest that lower preoperative fasting glucose levels enhance the likelihood of postoperative T2DM remission. Moreover, preoperative TG could potentially play a mediating role in the postoperative remission of T2DM. Therefore, evaluating and managing fasting glucose and lipids before the procedure may aid in assessing the prognosis of metabolic surgery. Level of evidence Level III, designed cohort.

Long non coding RNA COX10-DT promotes the progression of breast cancer via the COX10-DT/miR-206/BDNF axis.

Long noncoding RNAs (lncRNAs) are emerging as critical regulators in the biological development of breast cancer. In this study, we aimed to determine the roles and mechanisms of the lncRNA COX10 divergent transcript (COX10-DT) in breast cancer progression. The relative expression level of COX10-DT was calculated in matched breast cancer tissues and adjacent normal tissues using quantitative real-time PCR. Gain-of-function and loss-of-function approaches further revealed the functions and mechanisms of COX10-DT in breast cancer cells. Clinically, we found that the lncRNA COX10-DT was commonly overexpressed in breast cancer tissues compared to paired peritumoural tissues. Functionally, the lncRNA COX10-DT might promote the proliferation and migration of breast cancer cells. Mechanistically, the lncRNA COX10-DT did not play a role by regulating the expression of its divergent gene COX10 but acted as a competitive endogenous RNA (ceRNA) by directly sponging miR-206, which further regulated the expression of brain-derived neurotrophic factor (BDNF). Taken together, our results proved that the lncRNA COX10-DT could function via the COX10-DT/miR-206/BDNF axis, thereby promoting the development of breast cancer. These findings indicated that the lncRNA COX10-DT might be a potential biomarker and therapeutic target for breast cancer.

Incidence and survival of adenocarcinoma with mixed subtypes in patients with colorectal cancer.

BACKGROUND: Limited attention was paid to adenocarcinoma with mixed subtypes (AM) of the colon and rectum due to its low incidence. This study aims to assess the frequency and survival rates of tumors in the population. METHODS: The data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019. The incidence of tumors was evaluated based on patient gender, age, race, and location. Univariate and multivariate Cox analyses were performed to identify risk factors associated with tumor survival. Additionally, a nomogram was constructed using these risk factors to predict cancer-specific survival (CSS) at 1, 2, and 3 years. Receiver operating characteristic (ROC) and calibration curves were applied to examine the model's accuracy. RESULTS: The overall incidence of colorectal AM reached its highest level in 2016 (2.350 (95% CI: 2.241-2.462)). AM is more frequent in elderly patients and predominantly located in the rectum. By forest plot for multivariable Cox regression analysis, patient age, the number of regional positive lymph nodes and lymph nodes removed, tumor N/M stage, and postoperative chemotherapy were identified as independent risk indicators for CSS. Nomogram was constructed and validated as a feasible prediction model of CSS in patients with colorectal AM. CONCLUSION: The presence of colorectal AM in elderly patients, particularly in the rectum, is frequent and often associated with poor prognosis. Our nomograms can offer a relatively accurate prediction of CSS of patients with AM after tumor resection.

ncRNAs-mediated high expression of TIMM8A correlates with poor prognosis and act as an oncogene in breast cancer.

BACKGROUND: Breast cancer is notorious for its increasing incidence for decades. Ascending evidence has demonstrated that translocase of inner mitochondrial membrane (TIMM) proteins play vital roles in progression of several types of human cancer. However, the biological behaviors and molecular mechanisms of TIMM8A in breast cancer remain not fully illustrated. METHODS: Pan-cancer analysis was firstly performed for TIMM8A's expression and prognosis by Oncomine database. Subsequently, TIMM8A-related noncoding RNAs (ncRNAs) were identified by a series of bioinformatics analyses and dual-luciferase reporter assay, including expression analysis, correlation analysis, and survival analysis. Moreover, the effect of TIMM8A on breast cancer proliferation and apoptosis was evaluated in vitro by CCK-8 assays, EdU cell proliferation assays, JC-1 mitochondrial membrane potential detection assays and Western blot assays and the in vivo effect was revealed through a patient-derived xenograft mouse model. RESULTS: We found that TIMM8A showed higher expression level in breast cancer and the higher TIMM8A mRNA expression group had a poorer prognosis than the lower TIMM8A group. hsa-circ-0107314/hsa-circ-0021867/hsa-circ-0122013 might be the three most potential upstream circRNAs of hsa-miR-34c-5p/hsa-miR-449a-TIMM8A axis in breast cancer. TIMM8A promotes proliferation of breast cancer cells in vitro and tumor growth in vivo. CONCLUSION: Our results confirmed that ncRNAs-mediated upregulation of TIMM8A correlated with poor prognosis and act as an oncogene in breast cancer.

Circular RNA circ_0001017 Sensitizes Cisplatin-Resistant Gastric Cancer Cells to Chemotherapy by the miR-543/PHLPP2 Axis.

Resistance to cisplatin (CDDP) remains a major challenge for the treatment of gastric cancer (GC). Circular RNAs (circRNAs) have been implicated in the development of CDDP resistance of GC. However, the precise actions of circ_0001017 in CDDP resistance of GC remain to be elucidated. The levels of circ_0001017, microRNA (miR)-543 and PH-domain and leucine-rich repeat protein phosphatase 2 (PHLPP2) mRNA were gauged by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was used to analyze the protein levels of Vimentin, N-cadherin, E-cadherin, and PHLPP2. Ribonuclease R (RNase R) assay was applied to evaluate the stability of circ_0001017. Cell viability and proliferation, colony formation ability, cell cycle distribution and apoptosis, and migration and invasion were detected by the Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and transwell assays, respectively. Direct relationship between miR-543 and circ_0001017 or PHLPP2 was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft model assay was used to assess the function of circ_0001017 in vivo. Low expression of circ_0001017 was associated with CDDP resistance of GC. Enforced expression of circ_0001017 impeded growth, metastasis, and enhanced apoptosis of HGC-27/R and AGS/R cells and sensitized them to CDDP in vitro. Circ_0001017 targeted miR-543, and circ_0001017 regulated CDDP-resistant cell behaviors and CDDP sensitivity by suppressing miR-543. PHLPP2 was a direct target of miR-543, and circ_0001017 controlled PHLPP2 expression through miR-543. Moreover, miR-543 knockdown-mediated promotion of PHLPP2 impacted CDDP-resistant cell behaviors and CDDP sensitivity in vitro. Additionally, elevated expression of circ_0001017 hindered growth of HGC-27/R cells and sensitized them to CDDP in vivo. Our findings demonstrated that enforced expression of circ_0001017 suppressed malignant behaviors and enhanced CDDP sensitivity of CDDP-resistant GC cells at least partially by the miR-543/PHLPP2 axis.

A Bilevel Optimization Model Based on Edge Computing for Microgrid.

With the continuous progress of renewable energy technology and the large-scale construction of microgrids, the architecture of power systems is becoming increasingly complex and huge. In order to achieve efficient and low-delay data processing and meet the needs of smart grid users, emerging smart energy systems are often deployed at the edge of the power grid, and edge computing modules are integrated into the microgrids system, so as to realize the cost-optimal control decision of the microgrids under the condition of load balancing. Therefore, this paper presents a bilevel optimization control model, which is divided into an upper-level optimal control module and a lower-level optimal control module. The purpose of the two-layer optimization modules is to optimize the cost of the power distribution of microgrids. The function of the upper-level optimal control module is to set decision variables for the lower-level module, while the function of the lower-level module is to find the optimal solution by mathematical methods on the basis of the upper-level and then feed back the optimal solution to the upper-layer. The upper-level and lower-level modules affect system decisions together. Finally, the feasibility of the bilevel optimization model is demonstrated by experiments.

ETV4 transcriptionally activates HES1 and promotes Stat3 phosphorylation to promote malignant behaviors of colon adenocarcinoma.

Colon adenocarcinoma (COAD) is the commonest type of colorectal cancer with high morbidity and mortality worldwide. ETS variant 4 (ETV4) is a member of the ETS transcription factors and is frequently involved in the progression of many cancers. This study focused on the relevance of ETV4 to the progression of COAD. ETV4 was highly expressed in the collected COAD tissues and acquired cells and indicated advanced Dukes staging in patients. Knockdown of ETV4 in COAD cells weakened proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) activity of cells. The downstream genes of ETV4 were predicted, and a Gene Ontology (GO) analysis was conducted to identify the key molecule involved. ETV4 bound to the promoter sequence of HES1 and activated its transcription. Further overexpression of HES1 restored the malignant behaviors of COAD cells. HES1 was also found to promote phosphorylation of Stat3. Similar results were reproduced in vivo where downregulation of ETV4 blocked the growth of xenograft tumors in nude mice. This study demonstrated that ETV4 encourages malignant development of COAD through activating HES1 transcription and Stat3 phosphorylation. This study may offer novel insights into COAD therapy.

LINC02535 promotes cell growth in poorly differentiated gastric cancer.

BACKGROUND: Abnormal long non-coding RNA (lncRNA) expression plays important roles in gastric cancer. However, the functions of many lncRNAs in poorly differentiated gastric cancer (PDGC) remain unknown. METHODS: Three sets of paired tissues from patients with PDGC were used, and transcriptome sequencing was performed, followed by the construction and sequencing of a library and mapping of the reads. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and protein-protein interaction (PPI) networks were analysed, and canonical pathway significance was calculated among the differentially expressed genes (DEGs; p < 0.05). Gene expression in 30 paired PDGC specimens and four cell lines was validated through quantitative PCR. Cell proliferation, migration, invasion, apoptosis, and wound healing were analysed. RESULTS: A total of 499 upregulated DEGs and 627 downregulated DEGs were identified between peritumoral and gastric cancer tissues. The proportions of positive and negative correlations between LINC02535 and the DEGs were 98.40% and 92.66%, respectively, while the Spearman's correlation coefficient was greater than 0.5. The PPI network showed that approximately 73.15% of the top five genes were directly correlated with LINC02535 according to the STRING database. Based on KEGG analysis, the functions of LINC02535 target genes were enriched in signalling pathways related to cancer cell growth. Furthermore, cell function studies showed that LINC02535 upregulation contributed to cell proliferation, migration, invasion, and wound healing and that its inhibition facilitated cell apoptosis. CONCLUSION: LINC02535 expression was upregulated in PDGC and contributed to cell proliferation, migration, invasion and wound healing, whereas its inhibition in PDGC facilitated cell apoptosis.

Involvement of acid-sensing ion channel 1a in gastric carcinoma cell migration and invasion.

Acidic microenvironment, particularly acid-sensing ion channel 1a (ASIC1a), has been reported to promote carcinoma cell proliferation as well as migration. In this study, we explored the effect of ASIC1a on migration and invasion of gastric carcinoma (GC). ASIC1a expression levels were examined in paired GC and adjacent normal tissues from 16 patients by immunohistochemistry. Reverse transcription real-time PCR and immunoblotting were conducted to assess the ASIC1a expression levels in the GC cell line AGS after transfection with ASIC1a small hairpin RNA (shRNA). Wound healing and transwell invasion assays were utilized to detect metastasis and invasion following ASIC1a silencing. Tumor formation was used to detect the role of ASIC1a in tumorigenicity in vivo. It was found that ASIC1a expression level was significantly higher in GC tissues showing postoperative metastasis compared with non-metastasis and non-tumor tissues. Moreover, silencing of ASIC1a with shRNA significantly down-regulated ASIC1a expression and reduced GC cell migration and invasion. A moderately acidic extracellular environment inhibited GC cell viability. Furthermore, ASIC1a shRNA caused inhibition of tumorigenicity in vivo. Our study is the first report of attenuating the malignant phenotype of GC in vitro and in vivo by suppressing ASIC1a, and suggests a novel approach to study the relationship between ASICs and GC cell migration and invasion.

Clinical application of the dissection of the preperitoneal space without electrocoagulation in laparoscopic transperitoneal inguinal hernia repair throughout of the whole process.

Introduction: The dissection of the preperitoneal space is performed using a monopolar instrument to prevent bleeding in laparoscopic transabdominal preperitoneal hernia repair (TAPP). It may also cause energy injuries and nerve damage. Aim: To assess the effectiveness and safety of dissection of the preperitoneal space without electrocoagulation (DPSWE) in TAPP throughout the process. Material and methods: A retrospective analysis of data of 134 patients was made. The electrocoagulation group (EG) relied on monopolar instruments. In the non-electrocoagulation group (NEG) mainly scissors were used without electrocoagulation. The patients were followed for up for 3 months. Intraoperative and postoperative conditions and other complications were observed. Results: The VAS scores in the NEG were lower than those in the EG (p < 0.05). The operation time in the NEG was shorter than that in the EG (p < 0.05). Hospitalization expenses, scrotal seroma formation, and rupture of hernia sac in the NEG were lower than those in the EG (p < 0.05). The intraoperative bleeding volume above 20 ml in the NEG was higher than that in the EG. There was no significant difference in the incidence of postoperative bleeding, vas deferens injury, intestinal injury, surgical site infection, length of hospital stay, urinary retention and hernia recurrence in the NEG and the EG (p > 0.05). There was no significant difference in the incidence of surgical site infections (SSIs) in the NEG and the EG. Conclusions: DPSWE is effective and safe. DPSWE may reduce postoperative pain and have no significant increase in postoperative bleeding.

Survival and Prognosis for Patients with Rectal Melanomas in the United States: A SEER-Based Study.

PURPOSE: Limited attention was paid to focus on rectal melanomas (RM). This study aimed to evaluate the survival rate and prognostic factors of RM. METHODS: The data for patients with RM from Surveillance, Epidemiology, and End Results (SEER) database were used to analyze tumor survival. Kaplan-Meier method and log-rank test were employed to estimate cancer-specific survival (CSS) and overall survival (OS). A nomogram was established based on the risk factors of survival by the forest plot for multivariate Cox regression analysis. Receiver operating characteristic (ROC) and calibration curve were conducted for validation. RESULTS: A total of 187 patients with RM were selected to perform survival analyses. The median survival time of OS was 12 months (range: 0-146 months), and the median survival time of CSS was 12 months (range: 0-74 months). Patients' age, tumor size, stage, the number of nodes examined, surgery, and radiation were identified as prognostic indicators for CSS by the forest plot for multivariate Cox regression analysis. The nomogram was validated as a reliable model for CSS. CONCLUSION: Clinicopathologic relevance with tumor prognosis was confirmed in this study. Our nomogram can provide a relatively accurate prediction of the survival rate of patients with RM.

Pathological and immunohistochemical analysis of gastric mucosa after one anastomosis gastric bypass surgery.

BACKGROUND: One anastomosis gastric bypass (OAGB) is now the third most common bariatric surgery worldwide. This procedure is garnering increasing attention, but its complication of bile reflux and the associated risk of gastric carcinogenesis remains controversial. OBJECTIVE: The study aims to assess the impact of bile reflux on the gastric mucosa by comparing pathological and immunohistochemical results of gastric mucosa before and 2 years after OAGB surgery. METHODS: This retrospective study analyzed gastric lesions observed in gastroscopy before and after OAGB surgery. Pathological examinations were conducted on mucosal samples from proximal, middle and distal part of stomach, with a particular focus on the expression of Ki-67, P53, and CDX2 in immunohistochemistry. Ki-67 indicates cellular proliferation, P53 is a tumor suppressor protein, and CDX2 is a marker for intestinal differentiation. RESULTS: A total of 16 patients completed the follow-up. Regarding gastritis, presurgery nonerosive gastritis was found in two cases (12.5%), and postsurgery in six cases (37.5%). Erosive gastritis increased from one case (6.2%) presurgery to three cases (18.7%) postsurgery, totaling an increase from three to nine cases (p = .028). Bile reflux in the stomach increased from one case (6.2%) presurgery to three cases (18.7%) postsurgery. Most lesions in the proximal, middle, and distal part of stomach were relatively mild, with normal tissue states being predominant. Mild inflammation was found in all three areas, whereas moderate inflammation, intestinal metaplasia, and glandular atrophy were less common. No cases of severe inflammation were noted. The expression of gastric biomarkers CDX-2, Ki67, and P53 showed no significant statistical variation in different areas. CONCLUSION: Bile reflux does occur after OAGB, but its incidence is not high. Based on the immunohistochemical and pathological results of the gastric mucosa 2 years post-OAGB, there seems to be no significant causal relationship between OAGB and oncogenic inflammation around the gastric tube.

Transumbilical Stapling Technic of OAGB.

Single-port or single-incision laparoscopic surgery (SILS) is esteemed for its efficacy in achieving superior postoperative cosmetic outcomes compared to the conventional laparoscopic approach (Behnia-Willison et al. in Aust N Z J Obstet Gynaecol 52:366-370, 2012; Rogula et al. in Obes Surg 24:1102-1108, 2014; Pitot et al. in Surg Endosc 28:3007-3011, 2014). The introduction of SILS for bariatric procedures can be attributed to the pioneering work of Saber in 2008, who initially applied this technique to laparoscopic sleeve gastrectomy (SG), followed by its utilization in laparoscopic adjustable gastric banding (AGB) (Saber et al. in Obes Surg 18:1338-1342, 2008;Nguyen et al. in Obes Surg 18:1628-1631, 2008). The inaugural application of SILS in Roux-en-Y gastric bypass (RYGB) was documented in 2009, employing a plastic reconstruction methodology. Acknowledging the intricate nature of complex bariatric interventions, we previously detailed a modified SILS approach termed the transumbilical two-site (TUTS) technique for RYGB, which was established as a standard procedure in 2010 (Lee et al. in Surg Obes Relat Dis. 8:208-13, 2012). At that juncture, a solitary article surfaced in 2010 elucidating the dimensions of the small gastric pouch as a mere 8-9 cm, falling short of contemporary surgical requisites for optimal outcomes in one anastomosis gastric bypass (OAGB) (Tacchino et al. in Obes Surg 20:1154-1160, 2010). Notably, the TUTS technique, which was successfully implemented for RYGB, had hitherto not been extended to OAGB due to the complexities associated with creating a slender gastric tube spanning 25 cm. In a pioneering development this year, we have devised a novel strategy to surmount this challenge. The present study is designed to expound upon the transumbilical stapling technique tailored to the unique demands of OAGB.

Sleeve gastrectomy with one anastomosis bipartition versus one anastomosis gastric bypass: A pilot study.

BACKGROUND: One anastomosis gastric bypass (OAGB) is a new recognized metabolic surgery, but the problem that we cannot screen the excluded stomach is a troubling issue in China. The emergence of sleeve gastrectomy plus one anastomosis bipartition (SG + OAB) makes us see a hope to solve this problem. OBJECTIVES: By comparing the efficacy of the two surgical methods, to evaluate whether SG + OAB surgery can solve the dilemma faced by OAGB that the excluded stomach cannot be screened. METHODS: A retrospective study to compare the patients who underwent OAGB and SG + OAB was conducted. The main outcome measures were (1) operation risk, (2) weight loss, and (3) diabetes remission at 6 months. RESULTS: This study was conducted in the bariatric/metabolic surgical center. From November 2021 to February 2022, a total of 30 patients with obesity who received SG + OAB surgery were recruited. Another matched 60 patients undergoing OAGB were recruited as control group. There was no difference in preoperative age (32.15 ± 9.02 vs. 34.47 ± 7.22; p = .224), female ratio (83% vs. 85%; p = .837), and BMI (36.18 ± 5.30 vs. 34.68 ± 5.58; p = .217) between the two groups. OAGB had a shorter mean operation time (121.67 ± 20.41 vs. 143.50 ± 25.07 min; p < .001) and a lower intraoperative blood loss (21.92 ± 12.35 vs. 32.43 ± 22.01 mL; p = .005), but a longer postoperative flatus passage (2.13 ± 0.43 vs. 1.87 ± 0.43 days; p = .007) compared with the SG + OAB group. Two patients (6.7%) developed major surgical complication in SG + OAB group but no major complication developed in OAGB group. At 6 months after surgery, SG + OAB had a higher %total weight loss than OAGB (31.05 ± 3.12 vs. 28.14 ± 5.43%; p = .015), but diabetes remission rate was similarly high in both groups. CONCLUSIONS: SG + OAB operation had a non-inferior or even better weight loss than OAGB, with a similar glycemic control efficacy. However, the high complication rate of SG + OAB is the major drawback that needs attention.

Clinicopathologic and prognostic factors of patients with T3/T4 colorectal signet ring cell carcinoma: a population-based study.

BACKGROUND: To evaluate cancer-specific survival (CSS) and construct a nomogram to predict the CSS of patients with colorectal signet ring cell carcinoma (SRCC). METHODS: The data for patients with colorectal SRCC from 2000 to 2019 was identified from Surveillance, Epidemiology, and End Results (SEER) database. Propensity Score Matching (PSM) was used to minimize bias between SRCC and adenocarcinoma patients. Kaplan-Meier method and log-rank test were used to estimate the CSS. A nomogram was constructed based on the independent prognostic factors identified by univariate and multivariate Cox proportional hazards regression analyses. The model was evaluated by receiver operating characteristic (ROC) curves and calibration plots. RESULTS: Poor CSS was more common in patients with colorectal SRCC, especially in patients with T4/N2 stage, tumor size > 80 mm, grade III-IV, and chemotherapy. Age, T/N stage, and tumor size > 80 mm were identified as independent prognostic indicators. And a prognostic nomogram was constructed and validated as an accurate model for the CSS of patients with colorectal SRCC by ROC curves and calibration plots. CONCLUSION: Patients with colorectal SRCC have a poor prognosis. And the nomogram was expected to be effective in predicting the survival of patients with colorectal SRCC.

LncRNA RUNX1-IT1 is downregulated in gastric cancer and suppresses the maturation of miR-20a by binding to its precursor.

BACKGROUND: RUNX1-IT1 has been characterized as a tumor suppressive long non-coding RNA (lncRNA) in several types of cancer but not gastric cancer (GC). This study aimed to explore the role of RUNX1-IT1 in GC. METHODS: The expression of RUNX1-IT1, microRNA (miR)-20a precursor and mature miR-20a in GC and healthy tissues donated by GC patients (n=62) were measured by RT-qPCR. Correlation analysis was performed by linear regression. The expression of mature miR-20a and miR-20a precursor in cells with overexpression of RUNX1-IT1 was also determined by RT-qPCR. Cell invasion and migration were evaluated by Transwell assays. RESULTS: RUNX1-IT1 was downregulated in GC. Across GC tissues, RUNX1-IT1 and mature miR-20a were inversely correlated. However, RUNX1-IT1 and miR-20a precursor were not closely correlated. RUNX1-IT1 and miR-20a precursor were predicted to interact with each other, and overexpression of RUNX1-IT1 in GC cells decreased the expression levels of mature miR-20a. Transwell assay showed that the enhancing effect of miR-20a on cell invasion and migration was reduced by overexpression of RUNX1-IT1. CONCLUSIONS: RUNX1-IT1 may suppress the GC cell movement by inhibiting the maturation of miR-20a.

Incidence, survival, and prognostic factors for patients with gastrointestinal mixed neuroendocrine non-neuroendocrine neoplasms: a SEER population-based study.

BACKGROUND: Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are a group of rare tumors with limited research currently available. This study aimed to analyze the incidence, survival, and prognostic factors of gastrointestinal MiNENs. METHODS: We included data from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019. We compared the clinicopathologic characteristics and survival rates between MiNENs and neuroendocrine tumors (NETs), and calculated the incidence of MiNENs. We utilized univariate and multivariate Cox analysis to assess independent factors of prognosis and established a nomogram to predict 1-, 2-, and 3-year cancer-specific survival (CSS). Calibration and receiver operating characteristic (ROC) curves were drawn to validate the accuracy and reliability of the model. Decision curve analysis (DCA) was used to assess the clinical utility of the model. RESULTS: Patients with gastrointestinal MiNENs had a poorer prognosis than those with NETs. The overall incidence of gastrointestinal MiNENs has been increasing annually. Multivariate Cox regression analysis revealed that tumor size, lymph node metastasis, distant metastasis, and surgery were independent risk factors for CSS in MiNENs patients. Based on these risk factors, the 1-, 2-, and 3-year CSS nomogram model for MiNENs patients was established. Calibration, ROC, and DCA curves of the training and validation sets demonstrated that this model had good accuracy and clinical utility. CONCLUSION: Gastrointestinal MiNENs are rare tumors with an increasing incidence rate. The nomogram model is expected to be an effective tool for personalized prognosis prediction in MiNENs patients, which may benefit clinical decision-making.

Oncolytic vaccinia virus acts synergistically with anti-PD-L1 antibody to enhance the killing of colon cancer cells by CD8+ T cells.

Both oncolytic vaccinia virus (OVV) and anti-PD-L1 antibody hold promise in cancer immunotherapy. Herein, we aimed to explore the possible synergistic effects of OVV and anti-PD-L1 on the growth and metastasis of colon cancer (CC) in mouse models. Microarray profiling of CC-related genes was first conducted. Expression of PD-L1 in CC tissues was predicted by TCGA and verified by flow cytometry and RT-qPCR. Then, mouse CC cell lines stably carrying luciferase MC38-luc and CT26-luc were infected with recombinant double-deleted vaccinia virus (vvDD) to evaluate the effect of vvDD on cell viability. The data indicated that PD-L1 was highly expressed in CC tissues and cells following vvDD infection. MC38-luc cells were inoculated into mice to construct CC-bearing mouse models, which were treated with vvDD or combined with anti-PD-L1, with tumor growth, metastasis, survival, and the immune environment analyzed. It was found that OVV combined with anti-PD-L1 antibody led to lower tumor burden and growth and higher survival rates than individual treatment in CC-bearing mice. In addition, this combination exerted a remote effect on the untreated subcutaneous tumors in the lateral abdomen, thus suppressing the tumor metastasis. Furthermore, combined therapy of OVV with anti-PD-L1 antibody activated CD8+ T cells, reduced exhaustion of CD8+ T cells, and enhanced their immune response, strengthening the killing of CC cells and inhibiting tumor growth and metastasis. In conclusion, our findings provide mechanistic insights into the action and efficacy of OVV as an immunomodulatory agent combined with the anti-PD-L1 antibody for the treatment of CC.

Identification of HAGHL as a novel metabolic oncogene regulating human colorectal cancer progression.

PURPOSE: Cancer development remains the most challenging obstacle in colorectal cancer (CRC) treatment. The current study aims to identify and demonstrate novel oncogenes for CRC. METHODS: The CRC data of the Cancer Genome Atlas database and the Gene Expression Omnibus database were subjected to bioinformatics analysis to identify the novel potential diagnostic and prognostic biomarkers for CRC. Immunohistochemical assay, western blot, and quantitative PCR (qPCR) were used to analyze hydroxyacylglutathione hydrolase-like (HAGHL) gene expression in CRC tissues and cultured CRC cells. D-Lactate colorimetric assay was applied to determine concentration of D-lactate in supernatants from CRC tissues and cell culture medium. Cell counting kit-8 (CCK-8) assay, flow cytometry, tumor xenografts experiment, and TUNEL staining analysis were performed to evaluate the function of HAGHL in CRC. RESULTS: We comprehensively analyzed the CRC data of the Cancer Genome Atlas database and the Gene Expression Omnibus database, and identified several novel potential diagnostic and prognostic biomarkers for CRC, including HAGHL, DNTTIP1, DHX34, and AP1S3. The expression of HAGHL, the strongest oncogenic activity gene, is positively related to D-lactate levels in CRC tissues and negatively associated with patient prognosis. HAGHL downregulation suppressed the production of D-lactate and induced apoptosis, resulting in inhibition of cell proliferation in vitro. In vivo experiment showed that knockdown of HAGHL induced cell apoptosis and inhibited tumor growth. CONCLUSION: These findings suggest that HAGHL acts as a novel metabolic oncogene and demonstrate the underlying mechanism by which HAGHL regulates CRC progression, highlighting its utility as a diagnostic and prognostic factor and as a potential therapeutic target for the treatment of CRC.

Management and outcomes of gastric leak after sleeve gastrectomy: results from the 2010-2020 national registry.

BACKGROUND: Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting. METHODS: To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan-Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks. RESULTS: A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population ( P = 0.005, = 0.026, <0.001, and = 0.001, respectively). Moreover, 83.1% (59/71) of the leakage was near the esophagogastric junction region. Leakage healed in 64 (88.9%, 64/72) patients. The median healing time of acute and non-acute leaks was 5.93 months and 8.12 months, respectively. Acute leak (38/72, 52.8%) was the predominant type with a cumulative reoperation rate >50%, whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment ( P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor. CONCLUSIONS: Male sex, elevated waist circumference, hypoproteinaemia, and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.