Endoscopic ultrasound diagnosis system based on deep learning in images capture and segmentation training of solid pancreatic masses.

BACKGROUND: Early detection of solid pancreatic masses through contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) is important. But CH-EUS is difficult to learn. PURPOSE: To design a deep learning-based CH-EUS diagnosis system (CH-EUS MASTER) for real-time capture and segmentation of solid pancreatic masses and to verify its value in the training of pancreatic mass identification under endoscopic ultrasound (EUS). METHODS: We designed a real-time capture and segmentation model for solid pancreatic masses and then collected 4530 EUS images of pancreatic masses retrospectively, used for training and testing of this model at a ratio of 8:2. The model is loaded into the EUS host computer to establish the CH-EUS MASTER system. A crossover trial was then conducted to evaluate the model's value in EUS trainee training by successfully conducting two groups of EUS trainees in model learning and trainer-guided training. The intersection over union (IoU) and the time to find the lesion were used to evaluate the model performance metrics, and the Mann-Whitney test was used to compare the IoU and the time to find the lesion in different groups of subjects. Paired t-test was used to compare the effects before and after training. When α ≤ 0.05, it is considered to have a significant statistical difference. RESULTS: The model test showed that the model successfully captured and segmented the pancreatic solid mass region in 906 EUS images. The real-time capture and segmentation model had a Dice coefficient of 0.763, a recall rate of 0.941, a precision rate of 0.642, and an accuracy of 0.842 (when the threshold is set to 0.5), and the median IoU of all cases was 0.731. For the AI training effect, the average IoU of eight trainees improved from 0.80 to 0.87 (95% CI, 0.032-0.096; p = 0.002). The average time for identifying lesions in the pancreatic body and tail improved from 22.75 to 17.98 s (95% CI, 3.664-5.886; p < 0.01). The average time for identifying lesions in the pancreatic head and uncinate process improved from 34.21 to 25.92 s (95% CI, 7.661-8.913; p < 0.01). CONCLUSION: CH-EUS MASTER can provide an effect equivalent to trainer guidance in training pancreatic solid mass identification and segmentation under EUS.

Contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) MASTER: A novel deep learning-based system in pancreatic mass diagnosis.

BACKGROUND AND AIMS: Distinguishing pancreatic cancer from nonneoplastic masses is critical and remains a clinical challenge. The study aims to construct a deep learning-based artificial intelligence system to facilitate pancreatic mass diagnosis, and to guide EUS-guided fine-needle aspiration (EUS-FNA) in real time. METHODS: This is a prospective study. The CH-EUS MASTER system is composed of Model 1 (real-time capture and segmentation) and Model 2 (benign and malignant identification). It was developed using deep convolutional neural networks and Random Forest algorithm. Patients with pancreatic masses undergoing CH-EUS examinations followed by EUS-FNA were recruited. All patients underwent CH-EUS and were diagnosed both by endoscopists and CH-EUS MASTER. After diagnosis, they were randomly assigned to undergo EUS-FNA with or without CH-EUS MASTER guidance. RESULTS: Compared with manual labeling by experts, the average overlap rate of Model 1 was 0.708. In the independent CH-EUS video testing set, Model 2 generated an accuracy of 88.9% in identifying malignant tumors. In clinical trial, the accuracy, sensitivity, and specificity for diagnosing pancreatic masses by CH-EUS MASTER were significantly better than that of endoscopists. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were respectively 93.8%, 90.9%, 100%, 100%, and 83.3% by CH-EUS MASTER guided EUS-FNA, and were not significantly different compared to the control group. CH-EUS MASTER-guided EUS-FNA significantly improved the first-pass diagnostic yield. CONCLUSION: CH-EUS MASTER is a promising artificial intelligence system diagnosing malignant and benign pancreatic masses and may guide FNA in real time. TRIAL REGISTRATION NUMBER: NCT04607720.

Circular RNA KIF4A Promotes Liver Metastasis of Breast Cancer by Reprogramming Glucose Metabolism.

Background: Circular RNAs (circRNAs) regulate complex functional processes and play crucial roles in cancer development and progression. It was reported that circKIF4 regulates the progression of triple-negative breast cancer (TNBC). This study evaluates the role of circKIF4 in breast cancer distant metastasis and metabolic reprogramming. Methods: RT-qPCR was performed to verify the expression of circKIF4A in breast cancer, liver metastatic tissues, and cell lines. The function of circKIF4A in metastasis was evaluated both in vitro and in vivo through a series of experiments, including cell migration and glucose intake experiments. Additionally, we conducted molecular experiments to clarify the regulatory role of circKIF4A. We then conducted a Luciferase reporter assay and an RNA immunoprecipitation assay to identify the molecular interactions between circKIF4A and miRNA. Results: circKIF4A was overexpressed in breast cancer cell lines and tissues, inhibiting its expression and suppressing breast cancer growth and metastasis. Interestingly, we observed that circKIF4A reprogrammed the glucose metabolism of breast cancer, and silencing circKIF4A greatly affected glucose uptake and lactate production in breast cancer cells. miR-335 can be sponged by circKIF4A, which affected the expression of ALDOA/OCT4 protein and regulated HK2/PKM2 expression. Conclusions: This study demonstrated that the circKIF4A-miR-335-OCT4/ALDOA-HK2/PKM2 axis is critical to breast cancer metabolic reprogramming, indicating that this axis could be a novel therapeutic target for the treatment of liver metastasis of breast cancer.

HMOX1 promotes lung adenocarcinoma metastasis by affecting macrophages and mitochondrion complexes.

Background: Metastasis is the leading cause of lung adenocarcinoma (LUAD) patient death. However, the mechanism of metastasis is unclear. We performed bioinformatic analyses for HMOX1 (Heme oxygenase-1), aiming to explore its role in LUAD metastasis. Methods: Pan-cancer analysis was first used to identify the metastasis-associated role of HMOX1 in LUAD. HMOX1-related genomic alterations were then investigated. Based on functional enrichment, we systematically correlated HMOX1 with immunological characteristics and mitochondrial activities. Furthermore, weighted gene co-expression network analysis (WGCNA) was applied to construct the HMOX1-mediated metastasis regulatory network, which was then validated at the proteomic level. Finally, we conducted the survival analysis and predicted the potential drugs to target the HMOX1 network. Results: HMOX1 expression was significantly associated with epithelial-mesenchymal transition (EMT) and lymph and distant metastasis in LUAD. High HMOX1 levels exhibited higher macrophage infiltration and lower mitochondrial complex expression. WGCNA showed a group of module genes co-regulating the traits mentioned above. Subsequently, we constructed an HMOX1-mediated macrophage-mitochondrion-EMT metastasis regulatory network in LUAD. The network had a high inner correlation at the proteomic level and efficiently predicted prognosis. Finally, we predicted 9 potential drugs targeting HMOX1-mediated metastasis in LUAD, like chloroxine and isoliquiritigenin. Conclusions: Our analysis elaborates on the role of HMOX1 in LUAD metastasis and identified a highly prognostic HMOX1-mediated metastasis regulatory network. Novel potential drugs targeting the HMOX1 network were also proposed, which should be tested for their activity against LUAD metastasis in future studies.

CALD1 Modulates Gliomas Progression via Facilitating Tumor Angiogenesis.

Angiogenesis is more prominent in anaplastic gliomas and glioblastoma (GBM) than that in pilocytic and diffuse gliomas. Caldesmon (CALD1) plays roles in cell adhesion, cytoskeletal organization, and vascularization. However, limited information is available on mechanisms underlying the effect of CALD1 on the microvascular facilitation and architecture in glioma. In this study, we explored the role of CALD1 in gliomas by integrating bulk RNA-seq analysis and single cell RNA-seq analysis. A positive correlation between CALD1 expression and the gliomas' pathological grade was noticed, according to the samples from the TCGA and CGGA database. Moreover, higher CALD1 expression samples showed worse clinical outcomes than lower CALD1 expression samples. Biofunction prediction suggested that CALD1 may affect glioma progression through modulating tumor angiogenesis. The map of the tumor microenvironment also depicted that more stromal cells, such as endothelial cells and pericytes, infiltrated in high CALD1 expression samples. CALD1 was found to be remarkably upregulated in neoplastic cells and was involved in tumorigenic processes of gliomas in single cell sequencing analysis. Histology and immunofluorescence analysis also indicated that CALD1 associates with vessel architecture, resulting in glioma grade progression. In conclusion, the present study implies that CALD1 may serve as putative marker monitoring the progress of glioma.

A novel integrated system using patient-derived glioma cerebral organoids and xenografts for disease modeling and drug screening.

A physiologically relevant glioma tumor model is important to the study of disease progression and screening drug candidates. However, current preclinical glioma models lack the brain microenvironment, and the established tumor cell lines do not represent glioma biology and cannot be used to evaluate the therapeutic effect. Here, we reported a real-time integrated system by generating 3D ex vivo cerebral organoids and in vivo xenograft tumors based on glioma patient-derived tissues and cells. Our system faithfully recapitulated the histological features, response to chemotherapy drugs, and clinical progression of their corresponding parental tumors. Additionally, our model successfully identified a case from a grade II astrocytoma patient with typical grade IV GBM features in both organoids and xenograft models, which mimicked the disease progression of this patient. Further genomic and transcriptomic characterization was associated with individual clinical features. We have demonstrated the "GBM-&Normal-like" signature to predict prognosis. In conclusion, we developed an integrated system of parallel models from patient-derived glioma cerebral organoids and xenografts for understanding the glioma biology and prediction of response to chemotherapy drugs, which might lead to a new strategy for personalized treatment for this deadly disease.

Transumbilical endoscopic surgery in the diagnosis of ascites of unknown origin.

OBJECTIVE: To explore whether transumbilical endoscopic surgery (TUES) can effectively and safely elucidate the causes of ascites of unknown origin.
 Methods: A total of 23 consecutive patients with ascites of unknown origin who undertook TUES procedures in the Department of Gastroenterology of The Third Xiangya Hospital of Central South University between January 2014 and January 2016 were retrospectively investigated. Clinical manifestations, laboratory examinations and findings from radiological examinations and endoscopic investigations were noted before the procedure. Conditions of the abdominal cavity under endoscope, final diagnosis and outcome of patients were carefully recorded.
 Results: TUES procedure was successfully performed in all 23 patients with an operation time of (58.2±13.9) min. Twenty-two patients were undertaken biopsy on the nodules or masses that found in the abdominal cavity. Definite diagnoses were established in the overwhelming majority of patients (22/23). The most common causes of ascites for the 23 cases was tuberculosis (8 cases), followed by peritoneal carcinomatosis (6 cases), and pseudomyxoma peritonei (5 cases). Operation-related complications, such as postoperative bleeding, perforation, peritonitis, intraabdominal chronic abscesses, were not observed, except one case showed a transient moderate fever in 24 hours after operation. No mortality related to TUES occurred. We concluded that TUES was a feasible, economic and minimally invasive approach to access the peritoneal cavity.
 Conclusion: TUES combinated with biopsy can effectively elucidate the causes of ascites of unknown origin.

Correction to: Evaluation of 22G fine-needle aspiration (FNA) versus fine-needle biopsy (FNB) for endoscopic ultrasound-guided sampling of pancreatic lesions: a prospective comparison study.

The HTML version of this article was updated to indicate that the copyright is with The Author(s).

Inhibition of lncRNA NEAT1 suppresses the inflammatory response in IBD by modulating the intestinal epithelial barrier and by exosome-mediated polarization of macrophages.

Inflammatory bowel disease (IBD) is a multifactorial inflammatory disease, and increasing evidence has demonstrated that the mechanism of the pathogenesis of IBD is associated with intestinal epithelial barrier injury. Long non­coding RNAs (lncRNAs) are a class of transcripts >200 nucleotides in length with limited protein­coding capability. Nuclear paraspeckle assembly transcript 1 (NEAT1) is a recently identified nuclear­restricted lncRNA, which localizes in subnuclear structures, termed paraspeckles, and is involved in the immune response in a variety of ways. However, the function of NEAT1 in IBD remains to be fully elucidated. In the present study, reverse transcription­quantitative polymerase chain reaction assays were performed to determine the expression levels of NEAT1 lncRNA in IBD serum samples and tissues. Furthermore, the effect of NEAT1 on the cell permeability of colon cells was investigated via determination of trans­epithelial electrical resistance as well as performance of western blot and immunofluorescence assays. In addition, dextran sodium sulfate assays were performed to investigate the effect of downregulation of NEAT1 in IBD of mice. The present study detected the expression levels of NEAT1 in IBD cells and animal models to examine the changes in intestinal epithelial cell permeability following inhibition of the expression of NEAT1. In addition, phenotypic transformation was examined following different treatments in epithelial cells and macrophages. The results suggested that the expression of NEAT1 was high in IBD and was involved in the inflammatory response by regulating the intestinal epithelial barrier and through exosome­mediated polarization of macrophages. The downregulation of NEAT1 suppressed the inflammatory response by modulating the intestinal epithelial barrier and through exosome­mediated polarization of macrophages in IBD. The results of the present study revealed a potential strategy of targeting NEAT1 for IBD therapy.

Assessment of Quality of Life in Chinese Patients With Inflammatory Bowel Disease and their Caregivers.

BACKGROUND: Chronic diseases such as inflammatory bowel disease (IBD) usually affect the psychological status and health-related quality of life (HRQOL) of patients and their caregivers. The aim of this study was to evaluate the level of anxiety, depression, and HRQOL and find the risk factors predictive of HRQOL in IBD patients and their caregivers in a Chinese population. METHODS: One hundred four adult patients with IBD, 102 family caregivers, and 99 healthy controls were enrolled. They completed self-administered surveys related to QOL and psychological questionnaires, including the Short Inflammatory Bowel Disease Questionnaire (patients only), the Short Form-36 Health Survey (SF-36), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). RESULTS: Both the mean SAS total score and the mean SDS total score among the patients and the caregivers were found to be significantly higher than those among the general population (P < 0.05). Total SF-36 score was significantly different between the patients and the general population (P = 0.001), and between caregivers and the general population (P = 0.011). The result showed that the total SF-36 score of the patients had a significant negative correlation with SAS score in the patients (P = 0.040), SDS score in the patients (P = 0.004), annual income (P = 0.036), use of biologicals (P = 0.028), frequency of hospitalization in the last year (P = 0.033), and severity of IBD (P = 0.021). The total SF-36 score of the caregivers was significantly and negatively correlated with SDS score in the caregivers (P = 0.010), SDS score in the patients (P = 0.010), use of biologicals (P = 0.013), and frequency of hospitalization in the last year (P = 0.010) of the patients. CONCLUSIONS: A large proportion of IBD patients and their caregivers experience a high level of anxiety and depression and an impaired HRQOL. Higher levels of anxiety and depression, annual income, use of biologicals, higher frequency of hospitalization in the last year, and disease activity were independent predictors of reduced patient HRQOL; higher levels of depression in both caregivers and patients, use of biologicals, and frequency of hospitalization in the last year of the patients were independent predictors of reduced caregiver HRQOL.

Evaluation of 22G fine-needle aspiration (FNA) versus fine-needle biopsy (FNB) for endoscopic ultrasound-guided sampling of pancreatic lesions: a prospective comparison study.

BACKGROUND: To compare the diagnostic yield and safety of 22G endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) in the diagnosis of pancreatic solid lesions. METHODS: Between April 2014 and September 2015, 36 patients with pancreatic solid lesions were included for endoscopic ultrasound test. Patients were randomly divided into two groups: EUS-FNA (n = 18) and EUS-FNB (n = 18). Each nidus was punctured three times (15 ~ 20 insertions for each puncture) with a 22G needle. The core specimens were analyzed, and the diagnostic yields of FNA and FNB were evaluated. RESULTS: The procedure success rate was 100% with no complications. Cytological and histological examinations found that the diagnostic yield of FNB and FNA were both 83.3%. To get a definitive diagnosis, FNB needed fewer punctures than FNA (1.11 vs. 1.83; P  <  0.05). CONCLUSIONS: 22G EUS-FNB is a safe and effective way to diagnose pancreatic solid lesions. FNB required a lower number of needle passes to achieve a diagnosis compared with FNA.

Incomplete ileus and hemafecia as the presenting features of multi-organ involved primary systemic AL amyloidosis: a rare case report.

BACKGROUND: AL Amyloidosis is known to be a systemic disease affecting multiple organs and tissue while it's rare that patients present with gastrointestinal symptoms at first and later develop multiple-organ dysfuction. Clinical signs are not specific and the diagnosis is rarely given before performing immunofixation and endoscopy with multiple biopsies. We would like to emphasize the value of precise diagnostic process of AL amyloidosis. CASE PRESENTATION: In this case report, we describe a 56-year-old man who presented with recurrent periumbilical pain for 4 months and gradually worsened over a month. After a series of tests, he was finally diagnosed with primary systemic AL amyloidosis. He was treated with a chemotherapy regimen (Melphalan, dexamethasone and thalidomide) achieving a good clinical response. CONCLUSION: On account of the high misdiagnosis rate, establishing the most precise diagnosis in first time with typing amyloidogenic protein becomes increasingly vital. Although the presenting feature is usually nonspecific, AL amyloidosis ought to be considered when multiple organs are involved in a short period.

[Experience in transumbilical endoscopic surgery diagnosis for 3 cases of pseudomyxoma peritonei].

Three patients of pseudomyxoma peritonei who were diagnozed by transumbilical endoscopic surgery (TUES) were reviewed retrospectively from September 2014 to November 2014. Three cases of ascites patients underwent TUES were diagnozed as pseudomyxoma peritonei. All operations were successful. No open surgery or laparoscopic surgery was required. The mean operative time was (45±16) min; the mean intraoperative blood loss was 510 mL; the mean hospital stay time was 3 days. During the follow up of 911 months, no obvious scar was observed. Cosmetic results appear to be excellent. All patients were treated with intraperitoneal hyperthermia and chemotherapy. The survival rate was 100%. As a novel scarless endoscopic invasive abdominal surgery, TUES has high clinical value with the advantages such as small trauma, no scars, small risk and low cost in the diagnosis of unexplained ascites.

The tumor suppressor miR-138-5p targets PD-L1 in colorectal cancer.

microRNAs (miRNAs) play critical roles in cancer development and progression. This study investigated the effects of miR-138-5p in human colorectal cancer (CRC) development. miR-138-5p was frequently downregulated in CRC tissues and was associated with advanced clinical stage, lymph node metastasis and poor overall survival. We found that miR-138-5p decreased expression of programmed cell death ligand 1 (PD-L1) through interaction with its PD-L1 3' untranslated region. miR-138-5p also dramatically suppressed CRC cell growth in vitro and inhibited tumorigenesis in vivo. PD-L1 and miR-138-5p levels were inversely correlated in human CRC tumors, and miR-138-5p inhibited PD-L1 expression in tumor models. These results suggest that miR-138-5p is a tumor suppressor in CRC, and its effects are exerted at least partially through PD-L1 downregulation. Low miR-138-5p and high PD-L1 levels correlated with shorter overall CRC patient survival, indicating that miR-138-5p and PD-L1 may serve as CRC biomarkers for risk group assignment, optimal therapy selection and clinical outcome prediction. Targeting PD-L1, possibly by administering miR-138-5p mimics, might be a clinically effective anti-CRC therapeutic strategy.

[A case of complex Crohn's disease with severe complication].

Crohn's disease (CD) is a nonspecific chronic intestinal inflammatory disease with unknown etiology. The course of CD is persistent and recurrent. In the progress, CD can come with many complications such as obstruction, fistula formation, perforation, and hemorrhage. The early diagnosis, treatment, and the time of the surgery for CD pose a big controversy and challenge. There was a female patient diagnosed as Crohn's disease with severe complication in department of Gastroenterology of the Third Xiangya Hospital, Central South University.  We reported the diagnosis and treatment on this patient. The choice for the medicine and surgury was discussed.

miR-506 inhibits cell proliferation and invasion by targeting TET family in colorectal cancer.

OBJECTIVES: Ten-eleven translocation (TET) family members have been shown to be involved in the development of many tumors. However, the biological role of the TET family and its mechanism of action in colorectal carcinogenesis and progression remain poorly understood. MATERIALS AND METHODS: We measured the expression levels of TET family members in colorectal cancer (CRC) specimens, in the corresponding normal tissues and in cell lines using quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). Both the protein function and the protein-independent role of TETs were investigated by cell viability assays and cell invasion assays using in vitro and in vivo models. RESULTS: We found that all three TET genes were strongly up-regulated at the transcript level in CRC samples compared to matched normal tissues. The same results were observed in colorectal cancer cell lines. Knockdown of TETs by shTET1/2/3 showed that TET family members inhibited CRC growth and metastasis. We showed that TET family member degradation by miR-506 inhibits cell proliferation and invasion in colorectal cancer. CONCLUSION: Through this study, we advance our understanding of the expression levels TETs and miR-506 in CRC and further clarify the internal regulatory mechanism of miR-506 by targeting TET during CRC processes. These findings may contribute to a novel avenue for researching and developing targeted therapies for CRC.

[Application of endoscopic full-thickness resection in the treatment of gastric tumors originated fromthe muscularis propria].

OBJECTIVE: To evaluate the curative effect and safety of endoscopic full-thickness resection (EFR) in the treatment of gastric tumor originated from the muscularis propria.
 METHODS: Clinical data were collected from 34 patients, who underwent EFR of gastric tumor originated from muscularis propria, to observe the resection rate and complications from November 2012 to August 2014.
 RESULTS: Of the 34 patients, 15 were male, 19 were female, with the age of 38.3-70.6 (52.3±4.3) years old. The lesions of 25 patients located in the fundus of stomach and the rest was in the gastric body. EFR was successfully performed in the 34 patients with no need for surgery. The complete resection rate was 100%. Lesion diameter ranged from 1.0 to 5.0 (2.8±1.2) centimeters. The operation time was 50-100 (76.5±18.2) min. Patients with pneumoperitoneum were relieved after abdominal puncture exhaust, without post-operation bleeding and perforation. The hospitalization duration was 3-5 (3.6±0.8) days. Except 1 case, the remaining 33 cases were spindle cell tumors, consistent with the results of immunohistochemistry. The risk for two lesions with 4.5 cm and 5.0 cm was moderate. The risk of invasion was low or very low in the remaining 31 cases. Among them, 2 stromal tumors near the cardia showed a differentiation tendency toward smooth muscle. No lesion residual or recurrence happened during the follow-up period (range 5-23 months) in 34 cases. 
 CONCLUSION: EFR is a safe and effective method for gastric tumor originated from muscularis propria.

[Efficacy and safety of peroral endoscopic myotomy in the treatment of achalasia cardia].

OBJECTIVE: To evaluate the efficacy and safety of peroral endoscopic myotomy (POEM) for achalasia cardia (AC).
 METHODS: A total of 62 patients with AC were enrolled and treated with POEM in the Third Xiangya Hospital, Central South University from April 2012 to October 2014. The symptoms and complications were retrospectively analyzed.
 RESULTS: The ages of patients, including 32 males and 30 females, were 14-68 (43.2±5.6) years old. Eckardt scores were 4-6 or ≥7 for 25 patients or 37 patients (including 20 patients were at a score of 12). Thirteen patients suffered balloon expansion for 2-3 times. Sixty-one patients had completed POEM treatment, 1 patient were given Heller surgery instead of POEM because of extensive submucosal adhesion during POEM. The operative time for POEM was (60.8±15.1) min. Fourteen patients had mild subcutaneous emphysema. Among them, 5 suffered pneumoperitoneum and felt better after abdominal puncture exhaust; 2 patients suffered bronchospasm hypoxemia and were relieved after treatment by positive pressure oxygen for 1 h. The hospital stay was (4.3±1.2) d. The postoperative follow-up period was (11.4±5.4) months. Swallowing obstruction, vomiting and chest pain in patients was relieved at different degrees. The treatment effective rate was 100%. 
 CONCLUSION: POEM is a safe, effective and minimally invasive approach for AC.

Jak-STAT3 pathway triggers DICER1 for proteasomal degradation by ubiquitin ligase complex of CUL4A(DCAF1) to promote colon cancer development.

Chronic intestinal inflammation is closely associated with colon cancer development and STAT3 seems to take center stage in bridging chronic inflammation to colon cancer progress. Here, we discovered that DICER1 was significantly downregulated in response to IL-6 or LPS stimulation and identified a novel mechanism for DICER1 downregulation via proteasomal degradation by ubiquitin ligase complex of CUL4A(DCAF1) in colon cancer cells. Meanwhile, PI3K-AKT signaling pathway phosphorylated DICER1 and contributed to its proteasomal degradation. The regulation of DICER1 by CUL4A(DCAF1) affected cell growth and apoptosis which is controlled by IL-6 activated Jak-STAT3 pathway. Intervention of CUL4A(DCAF1) ubiquitin ligase complex led to fluctuation in expression levels of DICER1 and microRNAs, and thus affected tumor growth in a mouse xenograft model. A panel of microRNAs that were downregulated by IL-6 stimulation was rescued by siRNA-CUL4A, and their predicated functions are involved in regulation of cell proliferation, apoptosis and motility. Furthermore, clinical specimen analysis revealed that decreased DICER1 expression was negatively correlated with STAT3 activation and cancer progression in human colon cancers. DICER1 and p-STAT3 expression levels correlated with 5-year overall survival of colon cancer patients. Consequently, this study proposes that inflammation-induced Jak-STAT3 signaling leads to colon cancer development through proteasomal degradation of DICER1 by ubiquitin ligase complex of CUL4A(DCAF1), which suggests a novel therapeutic opportunity for colon cancer.

Application of clips assisted with foreign body forceps in defect closure after endoscopic full-thickness resection.

BACKGROUND: This study was designed to evaluate the feasibility and efficacy of metallic clips assisted with foreign body forceps closing the gastric wall defect after endoscopic full-thickness resection (EFR) for gastric submucosal tumors (SMTs). METHODS: Eighteen patients with gastric SMTs originated from the muscularis propria were treated by EFR between September 2012 and June 2014. Twelve patients underwent endoscopic closure of the gastric wall defects after EFR with endoloop and metallic clips (endoloop string suture method, ESSM), and six patients with clips and foreign body forceps (clips assisted with foreign body forceps clip method, CFCM). RESULTS: No significant differences existed between the two groups in terms of demographics, clinical characteristics, and the size of the gastric wall defects. The average time spent in closing the gastric wall defects (14.83 ± 1.94 min for the CFCM group and 22.42 ± 5.73 min for the ESSM group) and hospitalization fees of the CFCM group were significantly lower than those of the ESSM group. The average hospitalization time of the two groups had no statistical significance. No single case had surgical intervention or complications, such as gastric bleeding, perforation, peritonitis, or abdominal abscess. CONCLUSION: The CFCM and the ESSM are safe and effective techniques for gastric defect closure after EFR for gastric SMTs. Because of the "chopsticks effect," the CFCM more suitable for the lesions located at the gastric fundus, the greater curvature or anterior wall of the gastric body and gastric antrum.