Lantern-shaped flexible RNA origami for Smad4 mRNA delivery and growth suppression of colorectal cancer.

mRNA delivery has shown high application value in the treatment of various diseases, but its effective delivery is still a major challenge at present. Herein, we propose a lantern-shaped flexible RNA origami for mRNA delivery. The origami is composed of a target mRNA scaffold and only two customized RGD-modified circular RNA staples, which can compress the mRNA into nanoscale and facilitate its endocytosis by cells. In parallel, the flexible structure of the lantern-shaped origami allows large regions of the mRNA to be exposed and translated, exhibiting a good balance between endocytosis and translation efficiency. The application of lantern-shaped flexible RNA origami in the context of the tumor suppressor gene, Smad4 in colorectal cancer models demonstrates promising potential for accurate manipulation of protein levels in in vitro and in vivo settings. This flexible origami strategy provides a competitive delivery method for mRNA-based therapies.

Tranditional Roux-en-Y vs Uncut Roux-en-Y in Laparoscopic Distal Gastrectomy: a Randomized Controlled Study.

BACKGROUND: Traditional Roux-en-Y may cause Roux-en-Y stasis syndrome (RSS), and Uncut Roux-en-Y was proposed to solve this problem. However, because afferent loop recanalization may occur after surgery, its clinical application remains controversial. The purpose of this study was to compare the long-term outcomes of these two gastrointestinal reconstruction methods. METHODS: A total of 108 patients who received laparoscopic-assisted distal gastrectomy (LADG) were enrolled; 57 were randomly divided into the Uncut Roux-en-Y (URY) group, and 51 were divided into the Roux-en-Y (RY) group. Patients were followed up for 1 year to evaluate variables, including the following: (1) Assessments for RSS; (2) Preoperative and postoperative Gastrointestinal Symptom Rating Scale (GSRS) scores; (3) Postoperative gastroscopy to assess the occurrence of reflux esophagitis (Los Angeles classification), residual gastritis and bile reflux 1 year after surgery; and (4) Upper gastrointestinal radiography to evaluate whether recanalization occurred in patients in the URY group after surgery. RESULTS: At 1 year after surgery, a total of 42 patients (73.7%) developed afferent loop recanalization. The incidence of RSS was not different between the two groups (OR, 1.301 [95% CI, 0.482 to 3.509]; P = 0.603P = 0.603). The GSRS score was higher in the URY group (P < 0.001). Postoperative gastroscopy showed that the incidence of bile reflux (P < 0.001) and the grade of residual gastritis (P < 0.001) were significantly higher in the URY group, but the grade of reflux esophagitis was not significantly different (P = 0.447, [95% CI, 0.437 to 0.457]P = 0.397). CONCLUSIONS: Compared with traditional Roux-en-Y anastomosis, due to the high recanalization rate, the URY group developed more severe gastrointestinal symptoms, the incidence of bile reflux and the grade of residual gastritis increased and the incidence of postoperative RSS was not reduced.

Impact of endoscopic metallic stent placement and emergency surgery on detection of viable circulating tumor cells for acute malignant left-sided colonic obstruction.

BACKGROUND: Self-expanding metal stents (SEMS) served as a bridge to surgery (BTS). However, this method may be associated with worse long-term prognosis and relapse of CRC patients. Therefore, we attempted to clarify this in the angle of circulating tumor cells (CTCs). METHODS: A multicenter study was performed from March 2018 to January 2021. Thirty-two colorectal cancer patients with obstruction were selected, of which 21 patients were performed SEMS as a BTS while 11 patients were performed emergency surgery. Bloods samples were collected in two groups of patients for further detecting CTCs. In the SEMS group, the samples were collected before and after stent insert and after radical surgery performed. In the ES group, the samples were collected before stent insert and after emergency surgery performed. RESULTS: The number of CTCs did not show statistically significant differences before and after stent placement (34.90 vs 38.33, p=0.90), neither between the SEMS group and ES group in initial CTC levels (34.90 vs 58.09, p=0.394). No significant differences (38.33 vs 58.09, p=0.632) were observed after stent insert in the SMES group and the initial CTC levels in the ES group. Moreover, no major differences (24.17 vs 42.27, p=0.225) were observed after radical operation performed in both groups. CONCLUSION: The treatment of SEMS does not cause an increase in the number of CTC after stent insertion. Furthermore, there are may be other factors besides CTC to cause these poorer oncologic outcomes after SEMS placement.

Novel insight on predicting prognosis of gastric cancer based on inflammation.

Background: The tumor microenvironment (TME) and inflammation play vital roles in the development and progression of gastric cancer (GC). However, there are no inflammation-related models that can predict the prognosis and immunotherapy response of GC patients. We aimed to establish a prognostic model based on an inflammation-related gene (IRG) signature that can predict poor clinical outcomes in GC. Methods: We searched IRGs in The Cancer Genome Atlas (TCGA) database and identified genes differentially expressed in GC. The model was constructed using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analysis and validated using Gene Expression Omnibus (GEO) database. Receiver operating characteristic (ROC) curve, principal component analysis (PCA), and t-distribution stochastic neighbor embedding (t-SNE) analysis were performed to evaluate model performance. Independent prognostic factor, immune infiltration, cancer stemness, immunotherapy response analysis and gene set enrichment analysis (GSEA) were performed for functional evaluation. Results: An inflammation-related risk model was established based on 8 genes (F2, LBP, SERPINE1, ADAMTS12, FABP4, PROC, TNFSF18, and CYSLTR1). Risk score significantly correlated with poor outcomes and independently predicted prognosis. It was also associated with immune infiltration and reflected immunotherapy response. Conclusions: We established and validated an inflammation-related prognostic model that predicts immune escape and patient prognosis in GC. Our model is expected to improve clinical outcomes by facilitating clinical decision making and the development of individualized treatments.

Multi-omics analysis for potential inflammation-related genes involved in tumour immune evasion via extended application of epigenetic data.

Accumulating evidence suggests that inflammation-related genes may play key roles in tumour immune evasion. Programmed cell death ligand 1 (PD-L1) is an important immune checkpoint involved in mediating anti-tumour immunity. We performed multi-omics analysis to explore key inflammation-related genes affecting the transcriptional regulation of PD-L1 expression. The open chromatin region of the PD-L1 promoter was mapped using the assay for transposase-accessible chromatin using sequencing (ATAC-seq) profiles. Correlation analysis of epigenetic data (ATAC-seq) and transcriptome data (RNA-seq) were performed to identify inflammation-related transcription factors (TFs) whose expression levels were correlated with the chromatin accessibility of the PD-L1 promoter. Chromatin immunoprecipitation sequencing (ChIP-seq) profiles were used to confirm the physical binding of the TF STAT2 and the predicted binding regions. We also confirmed the results of the bioinformatics analysis with cell experiments. We identified chr9 : 5449463-5449962 and chr9 : 5450250-5450749 as reproducible open chromatin regions in the PD-L1 promoter. Moreover, we observed a correlation between STAT2 expression and the accessibility of the aforementioned regions. Furthermore, we confirmed its physical binding through ChIP-seq profiles and demonstrated the regulation of PD-L1 by STAT2 overexpression in vitro. Multiple databases were also used for the validation of the results. Our study identified STAT2 as a direct upstream TF regulating PD-L1 expression. The interaction of STAT2 and PD-L1 might be associated with tumour immune evasion in cancers, suggesting the potential value for tumour treatment.

CASC1 Expression in Bladder Cancer Is Regulated by Exosomal miRNA-150: A Comprehensive Pan-Cancer and Bioinformatics Study.

This study explored the role of cancer susceptibility 1 (CASC1) in tumorigenesis and development as well as the key pathways affecting bladder cancer progression. CASC1 was examined in various normal tissues in humans using the HPA database to quantify its expression level and subcellular localization. CASC1 is abundantly expressed in tumor tissues, primarily in cytoplasmic vesicles and stroma. TIMER2 was used to analyze the correlation between CASC1 expression levels and the types of infiltrates associated with immune cells and immunosuppressive cells. MDSC, Treg, M2, and CAF were significantly correlated with CASC1 expression in various tumors. Comparing patients with and without CASC1 mutation, those with CASC1 mutation had worse overall survival, progression-free survival, and disease-free survival. The correlation between has-miR-150 and CASC1 (for the case of bladder cancer) was then analyzed, and the related ceRNA network was mapped. A negative relationship between CASC1 expression and has-miR-150 expression was found in cases of bladder cancer. And the presence of miR-150-targeted CASC1 may be associated with bladder cancer progression. CASC1 is expressed at elevated levels in various tumor tissues, and it is associated with tumorigenesis and development. Exosomes containing miR-150-targeted CASC1 may affect the progression of bladder cancer.

Hollow CeO2 with ROS-Scavenging Activity to Alleviate Colitis in Mice.

INTRODUCTION: Excessive production of reactive oxygen species (ROS) to induce high oxidative stress is one of the main causes of colitis; thus, it has been regarded as a therapeutic target for colitis treatment. And the nanomaterial-based therapeutic strategies are effective against colitis. However, the previous elaborately designed materials exhibit limited application due to the uncertain biocompatibility and complicated manufacturing processes. METHODS: In this study, the highly monodisperse hollow CeO2 nanoparticles (H-CeO2) with uniform morphology were obtained by in situ growing CeO2 on solid silica nanoparticles and subsequently removing the silica core. The H-CeO2 was further modified with PEG, which owned excellent biological stability and biocompatibility. The experimental model of colitis induced by dextran sulfate sodium (DSS) was used to investigate the anti-inflammatory effect of H-CeO2-PEG. RESULTS: The H-CeO2-PEG showed good ROS scavenging efficacy and decreased the levels of proinflammatory cytokines (IL-6, IL-1ß, IL-18, and TNF-α) in DSS-induced colitis mice. Furthermore, H-CeO2-PEG inhibited the activation of the MAPK signalling pathway to alleviate colitis. CONCLUSION: This study reveals the therapeutic effects of CeO2-based nanomedicine toward colitis and elucidates the specific signalling pathway involved, which provides potential alternative therapeutic options for patients with inflammation tissue.

Recanalization in Uncut Roux-en-Y Reconstruction: An Animal Experiment and a Clinical Study.

Background: Because of the challenge of jejunal closure recanalization, uncut Roux-en-Y reconstruction remains controversial. This study aimed to investigate the incidence of recanalization after uncut Roux-en-Y reconstruction in pigs and a small number of patients. Methods: Twenty miniature pigs were subjected to distal gastrectomy and uncut Roux-en-Y reconstruction using various rows of linear staplers to block the intestine. The pigs were sacrificed, and the incidence of recanalization was investigated 1 month after the operation. From December 2018 to June 2019, 10 patients with gastric cancer who had undergone elective laparoscopy-assisted distal gastrectomy and uncut Roux-en-Y reconstruction were included in this study. The primary study outcome was recanalization of the afferent limb, demonstrated by gastrointestinal radiography 1, 3, and 6 months after surgery. Various numbers of staple lines across the afferent jejunal limb were applied for closure: 2 staple lines in 2 pigs, 4 staple lines in 6 pigs, 6 staple lines in 8 pigs, and 8 staple lines in 4 pigs. Results: Complete recanalization was detected in all 20 pigs 1 month postoperatively. Recanalization was detected in five cases (50%) by gastrointestinal radiography. Among them, 1 case of recanalization was found in the 1st month after the operation, 2 cases were found in the 3rd month, and another 2 cases were found in the 6th month. Bile reflux was detected by endoscopy in 2 patients with recanalization. Conclusions: The occurrence of afferent limb recanalization after uncut Roux-en-Y reconstruction is high, and using additional staplers alone cannot decrease the incidence of recanalization. Based on our study, uncut Roux-en-Y reconstruction is not recommended.

PLXNC1: A Novel Potential Immune-Related Target for Stomach Adenocarcinoma.

BACKGROUND: Gastric cancer is associated with tumor microenvironment and chronic inflammation, but the underlying tumor-promoting mechanisms still remain unknown. METHODS: The ATAC-seq was used to identify genes with chromatin accessibilities in promoter regions. The RNA-seq datasets were performed to identify differentially expressed genes (DEGs). Pearson correlation analysis with the mRNA expression of three families of tumor-related inflammation TFs was used to filter downstream DEGs. Cox univariate survival analysis was performed to identify the prognostic value. The ImmPort database and CIBERSORTx algorithm were used to investigate the regulatory relationship between hub DEGs and immune cells. Immunohistochemistry (IHC) and multidimensional database were performed to verification. RESULTS: In this case, we require 2,454 genes with chromatin accessibility in promoter regions by ATAC-seq. Based on the gene expression profiles (RNA-seq), we identified 365 genes with chromatin accessibility and differential expression. Combined with the Cox univariate survival analysis, we identified 32 survival-related DEGs with chromatin accessibility. According to ImmPort database, CXCL3, PLXNC1, and EDN2 were identified as immune- related genes in STAD. By applying the CIBERSORTx algorithm and Pearson correlation, PLXNC1 was the only gene correlated with various immune cells, significantly associated with M2 macrophages. Furthermore, gene set variation analysis (GSVA) suggests the "hallmark_interferon_gamma_response" pathway was most significantly correlated with PLXNC1. Immunohistochemistry results revealed that PLXNC1 protein level was significantly higher in STAD tissues than in normal tissues (p < 0.001). CONCLUSION: PLXNC1, regulated by IRF5, is an immune-related gene that was significantly associated with M2 macrophages and poor outcome in stomach adenocarcinoma.

Erratum: Chemopreventive effect of 4'-hydroxychalcone on intestinal tumorigenesis in ApcMin mice.

[This corrects the article DOI: 10.3892/ol.2021.12474.].

Propensity score-matched comparison of stenting as a bridge to surgery and emergency surgery for acute malignant left-sided colonic obstruction.

BACKGROUND: Bridge to elective surgery (BTS) using self-expanding metal stents (SEMSs) is a common alternative to emergency surgery (ES) for acute malignant left-sided colonic obstruction (AMLCO). However, studies regarding the long-term impact of BTS are limited and have reported unclear results. METHODS: A multicenter observational study was performed at three hospitals from April 2012 to December 2019. Propensity score matching (PSM) was introduced to minimize selection bias. The primary endpoint was overall survival. The secondary endpoints included surgical approaches, primary resection types, total stent-related adverse effects (AEs), surgical AEs, length of hospital stay, 30-day mortality and tumor recurrence. RESULTS: Forty-nine patients in both the BTS and ES groups were matched. Patients in the BTS group more often underwent laparoscopic resection [31 (63.3%) vs. 8 (16.3%), p < 0.001], were less likely to have a primary stoma [13 (26.5%) vs. 26 (53.1%), p = 0.007] and more often had perineural invasion [25 (51.0 %) vs. 13 (26.5 %), p = 0.013]. The median overall survival was significantly lower in patients with stent insertion (41 vs. 65 months, p = 0.041). The 3-year overall survival (53.0 vs. 77.2%, p = 0.039) and 5-year overall survival (30.6 vs. 55.0%, p = 0.025) were significantly less favorable in the BTS group. In multivariate Cox regression analysis, stenting (hazard ratio(HR) = 2.309(1.052-5.066), p = 0.037), surgical AEs (HR = 1.394 (1.053-1.845), p = 0.020) and pTNM stage (HR = 1.706 (1.116-2.607), p = 0.014) were positively correlated with overall survival in matched patients. CONCLUSIONS: Self-expanding metal stents as "a bridge to surgery" are associated with more perineural invasion, a higher recurrence rate and worse overall survival in patients with acute malignant left-sided colonic obstruction compared with emergency surgery.

Chemopreventive effect of 4'-hydroxychalcone on intestinal tumorigenesis in ApcMin mice.

Chalcones and its derivatives are reported to exhibit anti-cancer effects in several cancer cell lines, including colon cancer cells. However, the in vivo anticancer effects and associated mechanisms of chalcones against intestinal tumorigenesis currently remain unclear. The aim of the present study was to investigate the chemopreventive effect of a chalcone derivative, 4'-hydroxychalcone (4-HC), in a transgenic adenomatous polyposis coli multiple intestinal neoplasia mouse model (ApcMin) of spontaneous intestinal adenomas. ApcMin mice were fed 4-HC (10 mg/kg/day) or the vehicle control by oral gavage starting at 8 weeks of age, and were sacrificed at 20 weeks. The administration of 4-HC significantly decreased the number of colon adenomas by 45% and the size of colon adenomas by 35% compared with the respective controls. Similarly, the number of adenomas in the distal small intestine (DSI) and proximal small intestine also decreased by 35 and 33%, respectively, in 4-HC-treated mice, and adenoma size in the DSI decreased by 39% compared with the respective controls. Treatment with 4-HC strongly decreased proliferation in colon and DSI adenomas, as detected by immunofluorescence staining with the proliferation marker protein Ki-67, and promoted apoptosis in colon adenomas, as detected by TUNEL immunofluorescence staining. In addition, decreased mRNA expression of ß-catenin target genes, including c-Myc, Axin2 and CD44, in colon adenomas of 4-HC-treated animals demonstrated the involvement of the Wnt/ß-catenin signaling pathway in the initiation and progression of colon neoplasms. Treatment with 4-HC also decreased the protein levels of ß-catenin in colon adenomas, as demonstrated by immunofluorescence staining. The results suggested that 4-HC may be a promising candidate for the chemoprevention of intestinal tumorigenesis, and further investigations are required to evaluate its clinical utility.

Paneth cell-derived growth factors support tumorigenesis in the small intestine.

Paneth cells (PCs) are small intestinal epithelial cells that secrete antimicrobial peptides and growth factors, such as Wnt ligands. Intriguingly, the context in which PC-derived Wnt secretion is relevant in vivo remains unknown as intestinal epithelial ablation of Wnt does not affect homeostatic proliferation or restitution after irradiation injury. Considering the importance of growth factors in tumor development, we explored here the role of PCs in intestinal carcinogenesis using a genetic model of PC depletion through conditional expression of diphtheria toxin-α subunit. PC depletion in Apc Min mice impaired adenoma development in the small intestine and led to decreased Wnt3 expression in small bowel adenomas. To determine if PC-derived Wnt3 was required for adenoma development, we examined tumor formation after PC-specific ablation of Wnt3 We found that this was sufficient to decrease small intestinal adenoma formation; moreover, organoids derived from these tumors displayed slower growth capacity. Overall, we report that PC-derived Wnt3 is required to sustain early tumorigenesis in the small bowel and identify a clear role for PC-derived Wnt production in intestinal pathology.

Multi-Omics Analysis for Transcriptional Regulation of Immune-Related Targets Using Epigenetic Data: A New Research Direction.

Background: Currently, a comprehensive method for exploration of transcriptional regulation has not been well established. We explored a novel pipeline to analyze transcriptional regulation using co-analysis of RNA sequencing (RNA-seq), assay for transposase-accessible chromatin using sequencing (ATAC-seq), and chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq). Methods: The G protein-coupled receptors (GPCRs) possibly associated with macrophages were further filtered using a reduced-Cox regression model. ATAC-seq profiles were used to map the chromatin accessibility of the GPRC5B promoter region. Pearson analysis was performed to identify the transcription factor (TF) whose expression was correlated with open chromatin regions of GPRC5B promoter. ChIP-seq profiles were obtained to confirm the physical binding of GATA4 and its predicted binding regions. For verification, quantitative polymerase chain reaction (qPCR) and multidimensional database validations were performed. Results: The reduced-Cox regression model revealed the prognostic value of GPRC5B. A novel pipeline for TF exploration was proposed. With our novel pipeline, we first identified chr16:19884686-19885185 as a reproducible open chromatin region in the GPRC5B promoter. Thereafter, we confirmed the correlation between GATA4 expression and the accessibility of this region, confirmed its physical binding, and proved in vitro how its overexpression could regulate GPRC5B. GPRC5B was significantly downregulated in colon adenocarcinoma (COAD) as seen in 28 patient samples. The correlation between GPRC5B and macrophages in COAD was validated using multiple databases. Conclusion: GPRC5B, correlated with macrophages, was a key GPCR affecting COAD prognosis. Further, with our novel pipeline, TF GATA4 was identified as a direct upstream of GPRC5B. This study proposed a novel pipeline for TF exploration and provided a theoretical basis for COAD therapy.

Chromatin Accessibility Regulates Gene Expression and Correlates With Tumor-Infiltrating Immune Cells in Gastric Adenocarcinoma.

BACKGROUND: We explored key molecules affecting the prognosis of gastric adenocarcinoma (STAD) using co-analysis of chromatin accessibility (ATAC-seq), mRNA expression (RNA-seq), and overall survival. METHODS: We used the assay for transposase-accessible chromatin using sequencing (ATAC-seq) profiles to identify genes with chromatin accessibilities in their promoter regions. The RNA-seq profiles were processed for differentially expressed genes (DEGs) at mRNA level. The DEGs with chromatin accessibilities in promoter regions were further filtered using the Pearson correlation with TP53 expression. After co-analysis, genes were identified for the prognostic value using Kaplan-Meier method, followed by Pearson correlation analysis with significant pathways. For verification, we acquired clinical samples for qPCR and immunohistochemistry (IHC). Multidimensional database validations were performed to prevent the bias introduced by the use of a single database. RESULTS: We identified 11,557 DEGs and 57 genes with chromatin accessibilities. The co-analysis of ATAC-seq, RNA-seq, and clinical survival data revealed that interleukin-18 binding protein (IL18BP), with significant chromatin accessibility in its promoter region and differential mRNA expression, might be directly regulated by TP53 and influence STAD prognosis. Further, gene set variation analysis indicated that IL18BP may impact the survival of STAD patients in an immune-related manner. According to the CIBERSORT algorithm and Pearson correlation, the integration of IL18BP and CD4+ T memory cells may play an important role in the prognosis of STAD patients. CONCLUSION: IL18BP, regulated by TP53, may serve as a key molecule affecting STAD prognosis. And the mechanism is proposed to be the interaction between IL18BP and CD4+ T cells.

Comprehensive analysis of differentially expressed circRNAs revealed a ceRNA network in pancreatic ductaladenocarcinoma.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies. However, the molecular mechanisms underlying PDAC are still not completely understood. Circular RNAs (circRNAs) are a unique class of RNA formed by special loop splicing. More and more researchers have paid attention to circRNAs. MATERIAL AND METHODS: In this study, we constructed a circRNA-mediated competing endogenous RNA (ceRNA) network in PDAC. Gene ontology (GO) analysis was performed to explore circRNAs' potential roles in PDAC progression. We also constructed an up-stream transcriptional network of circRNAs' parental genes and found that many transcription factors (TFs), such as tumor protein p53 (TP53) and MYC, could regulate their expression. RESULTS: This study, which aimed to identify differentially expressed circRNAs in PDAC, suggested that circRNAs may also act as biomarkers for PDAC. We analyzed two public datasets (GSE69362 and GSE79634) to identify differentially expressed circRNAs in PDAC. Finally, we found that DExH-Box Helicase 9 (DHX9) may be a potential regulator of circRNA formation in PDAC. Genomic loci of four down-regulated circRNAs - hsa_circ_000691, hsa_circ_0049392, hsa_circ_0005203, and hsa_circ_0001626 - contained DHX9 binding sites, suggesting that they may be directly regulated by DHX9. CONCLUSIONS: Our study identified differentially expressed circRNAs in PDAC, suggesting that circRNAs may also act as biomarkers for PDAC. Additional investigations of function and up-stream regulation of differentially expressed circRNA in PDAC are still needed.

lncRNA CASC11 promotes cancer cell proliferation in bladder cancer through miRNA-150.

Long noncoding RNAs (lncRNAs) CASC11 is an oncogenic lncRNA in gastric cancer and colorectal cancer. Our study aimed to investigate the role of lncRNA CASC11 in bladder cancer. In this study we showed that plasma lncRNA CASC11 was upregulated, while plasma miRNA-150 was downregulated in patients with early-stage bladder cancer than in healthy controls. Altered expression of plasma lncRNA CASC11 and miRNA-150 separated patients with bladder cancer from healthy controls. lncRNA CASC11 expression was inversely correlated with miRNA-150 expression in patients with bladder cance but not in healthy controls. Overexpression of lncRNA CASC11 mediated the inhibition of miRNA-150 expression in cancer cells, while miRNA-150 overexpression did not significantly alter lncRNA CASC11 expression. lncRNA CASC11 overexpression promoted, while miRNA-150 overexpression inhibited cancer cell proliferation. miRNA-150 also attenuated the enhancing effects of lncRNA CASC11 overexpression on cancer cell proliferation. However, overexpression of lncRNA CASC11 showed no significant effects on cancer cell migration and invasion. Therefore, lncRNA CASC11 may promote cancer cell proliferation in bladder cancer, and the actions of lncRNA CASC11 are likely through miRNA-150.

[Clinical application of compound anastomotic device in protective terminal ileostomy during rectal cancer operation].

OBJECTIVE: To investigate the clinical effect of the application of "compound anastomotic device" on the high-risk colorectal anastomosis in rectal cancer patients undergoing protective ileostomy. METHODS: A total of 116 rectal cancer patients undergoing surgical procedure and prophylactic ileostomy in Tongji Hospital (90 cases) and The Third People's Hospital of Jingdezhen City (26 cases) from May 2011 to October 2016 were prospectively enrolled in the study. Paralleled control study and random digital table were applied. Fifty-eight cases received the compound anastomotic device for protective ileostomy (anastomosis ring group) and 58 cases underwent traditional terminal ileostomy (traditional group). The compound device was mainly composed of Valtrac biodegradable anastomosis ring, drainage tube and condom. Operational procedure was as follows: Ileocecum was freed through incision following laparoscopic total mesorectal excision; Two intestinal ring-shape purses were made; Intestinal wall between purse string was cut and the compound anastomotic device was put into; The purse was tightened and anastomosis ring was closed; The compound device was embed and pull out through the Trocar hole in the right lower abdomen; Then the drainage tube was fixed to the abdominal wall and connected with a drainage bag or an outer pocket. Incidence of anastomotic leak, stoma-related complications, hospital stay and total cost of two groups were compared. RESULTS: The general clinical data between two groups were not significantly different(all P>0.05). Stoma operation was performed successfully in all the patients of two groups. The stoma operation time was (34.6±13.8) min in anastomosis ring group and (25.8±14.0) min in traditional group with significant difference (t=2.123, P=0.035). Postoperative anastomotic leak occurred in 7 cases, including 3 cases with small fistula in traditional group and 4 cases in anastomosis ring group, of whom 1 case underwent left-low abdominal colonic stoma after necrotic intestine resection. All the patients were discharged within postoperative 7 to 37 days. In traditional group, 35 cases (60.3%) occurred stoma-related complications, the total hospitalization expenses was (65±28) thousand yuan, and the average hospital stay (including stoma reversion) was (23.6±11.8) days. In anastomosis ring group, 17 cases (29.3%) occurred stoma-related complications, the total hospitalization expense was (52±11) thousand Yuan, and the average hospital stay was (21.0±16.8) days. The incidence of anastomotic fistula and the hospital stay had no significant difference between two groups (all P>0.05). The stoma-related complication morbidity (χ2=3.216, P=0.002) and the total hospitalization expenses (t=2.683, P=0.027) in anastomosis ring group were significantly lower than those in traditional group. CONCLUSION: Compared with traditional ileostomy, the application of compound anastomotic device for protective ileostomy would be better to benefit the recovery of patients.

miR-224 Controls Human Colorectal Cancer Cell Line HCT116 Proliferation by Targeting Smad4.

Background: Better understanding the molecular mechanisms responsible for the genesis and progression of colorectal cancer would help advance the novel therapeutics. miR-224 has been identified to be elevated in colorectal cancer and promote human colorectal cancer cell line SW480 proliferation and invasion. However, the effect of miRNAs on cancer cell proliferation could be significantly changeable among different cell lines. HCT116 is a commonly used cell line for colorectal cancer study and the target gene responsible for the function of miR-224 in its proliferation is unclear. Methods: miR-224 expression was determined by quantitative reverse transcription polymerase chain reactions (PCRs) in human colorectal cancer tissues compared with their corresponding matched peritumoral tissues. HCT116 cell viability and cell proliferation were determined by CCK-8, EdU incorporation assays and flow cytometry for cell cycle. Target gene of miR-224 was confirmed by Western blots and siRNA for Smad4. Results: miR-224 was significantly increased by 29.49 fold in colorectal cancer tissues compared with their corresponding matched peritumoral tissues based on 12 colorectal cancer patients. miR-224 mimic significantly increased HCT116 cell viability, EdU positive cells rate, and decreased G1 phase cell population and increased S phase cell population. miR-224 inhibitor had opposite effects. Smad4 could be negatively regulated by miR-224 in HCT116 cells and was responsible for its effects in proliferation. Conclusion: miR-224 mediates HCT116 cell proliferation by targeting Smad4.

Influence of gum-chewing on postoperative bowel activity after laparoscopic surgery for gastric cancer: A randomized controlled trial.

BACKGROUND: In some studies, gum-chewing was demonstrated to have a beneficial effect on resumption of bowel function; however, other contradictory findings in other studies refute the effects of gum-chewing on peristaltic movements and digestive system stimulation. In addition, most previous studies were after colorectal or gynecology surgery, whereas few reports focused on the effect of gum-chewing after gastrectomy. The aim of this randomized controlled trial was to assess the effectiveness of gum-chewing on postoperative bowel function in patients who had undergone laparoscopic gastrectomy. METHODS: From March 2014 to March 2016, 75 patients with gastric cancer received elective laparoscopic surgery in Shanghai Tongji hospital and were postoperatively randomly divided into 2 groups: 38 in a gum-chewing (Gum) group and 37 in a control (No gum) group. The patients in the Gum group chewed sugarless gum 3 times daily, each time for at least 15 minutes, until the day of postoperative exhaust defecation. RESULTS: The mean time to first flatus (83.4 ±â€Š35.6 vs. 79.2 ±â€Š24.2 hours; P = 0.554) and the mean time to first defecation (125.7 ±â€Š41.2 vs. 115.4 ±â€Š34.2 hours; P = 0.192) were no different between the no gum and Gum groups. There was also no significant difference in the incidence of postoperative ileus (P = 0.896) and postoperative hospital stay (P = 0.109) between the 2 groups. The postoperative pain score at 48 hours (P = 0.032) in the Gum group was significantly higher than in the no gum group. There was no significant difference between the 2 groups in regards to patient demographics, comorbidities, duration of surgery, complications, and nausea/vomiting score. CONCLUSION: Gum-chewing after laparoscopic gastrectomy did not hasten the return of gastrointestinal function. In addition, gum-chewing may increase patient pain on the second postoperative day.