DendroX: multi-level multi-cluster selection in dendrograms.

BACKGROUND: Cluster heatmaps are widely used in biology and other fields to uncover clustering patterns in data matrices. Most cluster heatmap packages provide utility functions to divide the dendrograms at a certain level to obtain clusters, but it is often difficult to locate the appropriate cut in the dendrogram to obtain the clusters seen in the heatmap or computed by a statistical method. Multiple cuts are required if the clusters locate at different levels in the dendrogram. RESULTS: We developed DendroX, a web app that provides interactive visualization of a dendrogram where users can divide the dendrogram at any level and in any number of clusters and pass the labels of the identified clusters for functional analysis. Helper functions are provided to extract linkage matrices from cluster heatmap objects in R or Python to serve as input to the app. A graphic user interface was also developed to help prepare input files for DendroX from data matrices stored in delimited text files. The app is scalable and has been tested on dendrograms with tens of thousands of leaf nodes. As a case study, we clustered the gene expression signatures of 297 bioactive chemical compounds in the LINCS L1000 dataset and visualized them in DendroX. Seventeen biologically meaningful clusters were identified based on the structure of the dendrogram and the expression patterns in the heatmap. We found that one of the clusters consisting of mostly naturally occurring compounds is not previously reported and has its members sharing broad anticancer, anti-inflammatory and antioxidant activities. CONCLUSIONS: DendroX solves the problem of matching visually and computationally determined clusters in a cluster heatmap and helps users navigate among different parts of a dendrogram. The identification of a cluster of naturally occurring compounds with shared bioactivities implicates a convergence of biological effects through divergent mechanisms.

Hsa-circRNA-103809 Promotes Hepatocellular Carcinoma Development via MicroRNA-1270/PLAG1 Like Zinc Finger 2 Axis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death in the worldwide. A great number of reports manifested that circular RNA hsa-circRNA-103809 (circRNA-103809) could work in several cancers. AIMS: This study aimed to explore the function and mechanism of circRNA-103809 in HCC. METHODS: Gene expressions were detected by quantitative real-time polymerase chain reaction. Colony formation, cell counting kit-8, transwell and wound healing assays were implemented to check the role of circRNA-103809 in HCC. Subcellular fractionation analysis was designed to figure out the cellular location of circRNA-103809. Luciferase reporter assay and RNA pull down assay were employed to verify the relationships among RNAs. RESULTS: CircRNA-103809 was highly expressed in HCC cell lines. After interfering circRNA-103809, the proliferation, migration, invasion and epithelial-to-mesenchymal transition process were all hindered in HCC cells. Significantly, circRNA-103809 competed with PLAG1 like zinc finger 2 (PLAGL2) for binding with microRNA-1270 (miR-1270), which formulated a competing endogenous RNA network in HCC. Thereafter, we verified the tumor-facilitating effect of circRNA-103809/miR-1270/PLAGL2 axis on biological behaviors of HCC cells. CONCLUSION: Hsa-circRNA-103809 promoted development of HCC via sequestering miR-1270 and up-regulating PLAGL2.

miR-144 suppresses cell proliferation and migration in colorectal cancer by targeting NRAS.

Colorectal cancer (CRC) is a type of malignant cancer that has become particularly prevalent worldwide. It is of crucial importance to CRC treatment that the underlying molecular mechanism of CRC progression is determined. The NRAS gene is an important small G protein that is involved in various biological processes, including cancers. NRAS is an oncogene in many neoplasms but its function and regulation in CRC have seldom been investigated. In this study, it was uncovered that the NRAS protein was significantly upregulated in CRC tissues. According to a bioinformatics prediction, we identified that miR-144 may target NRAS to suppress its expression. In vitro experiments indicated that miR-144 decreased NRAS expression in different CRC cell lines (SW480, LoVo, and Caco2). By inhibiting NRAS, miR-144 repress SW480 cell proliferation and migration. Moreover, miR-144 decelerated the growth of SW480 xenograft tumors in vivo by targeting NRAS. In summary, our results identified a novel miR-144-NRAS axis in CRC that could promote the research and treatment of CRC.

microRNA-650 promotes inflammation induced apoptosis of intestinal epithelioid cells by targeting NLRP6.

Ulcerative colitis (UC), a serious threat to public health, is one of the main forms of inflammatory bowel disease, whereas the molecular mechanisms underlying ulcerative colitis induced by inflammation still remain elusive. NPLR6 gene is previously shown to regulate intestinal homeostasis and regulate the colonic microbial ecology. Here, we report that microRNA-650 (miR-650) plays an important role in the pathogenesis of UC as an upstream regulator of NPLR6 gene. MiR-650 is proved overexpressed in the inflamed mucosa of patients with ulcerative colitis and the DSS induced colitis model mice by qRT-PCR. Over-expression of miR-650 leads to increased apoptosis of Caco-2 and IEC-6 cells, and the DSS-induced mice aggravation, while knock-down of miR-650 shows opposite effects. Through constructing luciferase reporter genes containing 3'-untranslated regions of NLRP6, we further demonstrate that miR-650 inhibits NLRP6 through binding to its 3'-untranslated regions. Overexpression of NLRP6 in Caco-2 and IEC-6 cells suppress the increase apoptosis induced by miR-650 overexpression. Overall, the findings of this study indicate the role of miR-650 in ulcerative colitis, which provides a new target for therapeutic treatment.

scRNA-seq of colorectal cancer shows regional immune atlas with the function of CD20+ B cells.

Colorectal cancer (CRC) from different regions exhibits different histological, genetic characteristics, and molecular subtypes, even in response to conventional chemotherapies and immunotherapies. To characterize the immune landscape in different regions of CRC and search for potential therapeutic targets, we analyzed 39,484 single-cell transcription data from 19 samples of CRC and paired normal tissues from four regions to identify the immune characteristics of CRC among anatomic locations, especially in B cells. We discovered that immune cell infiltration in tumors significantly varied among different regions of CRC. B cells from right- and left-sided CRC had different development trajectories, but both had extensive interactions with myeloid cells and T cells. Survival analysis suggested that CD20+ B cells correlated with good prognosis in CRC patients, especially on the right side. Furthermore, the depletion of CD20+ B cells demonstrated that anti-CD20 promoted tumor growth progression and reversed the tumor-killing activity of anti-PD-1 treatment in vivo and in vitro. Our results highlight the characterization of the immune landscape of CRC in different regions. CD20+ B-cell infiltration has been associated with CRC patient prognosis and may promote the tumor-killing role of PD-1 antibodies.

FGFR2-TSC22D1, a novel FGFR2 fusion gene identified in a patient with colorectal cancer: A case report.

BACKGROUND: The FGFR signaling pathway is activated in multiple tumor types through gene amplifications, single base substitutions, or gene fusions. Novel FGFR gene fusions may represent candidate targets for the development of tyrosine kinase inhibitors. CASE SUMMARY: Herein, we report a patient with colorectal cancer (CRC) harboring a novel FGFR2 fusion gene. A 59-year-old man felt discomfort in his right upper abdomen with loss of appetite for 6 mo. An abdominal computed tomography scan revealed the existence of a space-occupying lesion in the ascending colon. The pathological diagnosis was a poorly differentiated adenocarcinoma. Subsequent biopsy specimen was subjected to next-generation sequencing analysis, and a novel FGFR2-TSC22D1 fusion with complete kinase structure of FGFR2 protein was identified. CONCLUSION: We report the first case of CRC harboring FGFR2-TSC22D1, which enriches the FGFR2 fusion spectrum. FGFR2 inhibitors might be effective in the later treatment for this patient.

Biomimetic enzyme barrier for preventing intestine-derived LPS induced diseases.

Biomimetic enzyme barrier (BEB) encapsulated microcapsules with alginate shells were in situ fabricated with a microfluidic electrospray approach for preventing intestine-derived LPS induced diseases. As the alginate shells could protect the contents in gastric juice and release them in the intestine, the inner BEB could form a consecutive immune barrier on the surface of the intestine during the release. Through combining BEB with alkaline phosphatase, the immune barrier could degrade and prevent the permeation of lipopolysaccharide, which enhanced the intestinal barrier function. Thus, the BEB microcapsules were imparted with outstanding ability in preventing intestine-derived LPS induced diseases. Based on an in vivo study, we demonstrated that this BEB microcapsule could effectively protect organ function, restore intestinal barrier integrity, prevent the permeation of LPS and alleviate inflammation. Therefore, the generated microcapsules have potential for clinical applications.

The Circumferential Resection Margin Is a Prognostic Predictor in Colon Cancer.

Objective: This study aimed to investigate the potential value of circumferential resection margin (CRM) in colon cancer prognostics. Summary Background Data: CRM has been extensively studied as an important prognostic factor in rectal and esophageal cancer, but not in colon cancer. Methods: Data from 6,681 CRM-positive patients and 25,908 CRM-negative patients diagnosed with colon cancer in 2010-2015 were obtained from the Surveillance, Epidemiology, and End Results database. Statistical analysis methods utilized included the chi-square test, Kaplan-Meier estimates, Cox proportional, and X-tile software analyses. Results: After propensity score matching, CRM positivity was found to be negatively related with survival (P < 0.001). X-tile software identified 0 and 30 mm as optimal cutoff values (P < 0.001) for prognosis, which was applicable only in stage II-IV patients. A 20 and 33% risk decrease were observed in patients with CRM between 0 and 30 mm [95% confidence interval (CI) = 0.76-0.84], and larger than 30 mm (95% CI = 0.62-0.71), respectively. Chemotherapy strongly benefited prognosis with a hazard ratio of 0.36 (95% CI = 0.34-0.38) for overall survival (OS). Patients with a CRM value of 0-30 mm seemed to benefit most from chemotherapy compared with other groups. CRM and number of regional lymph nodes are independent risk factors, and the latter is a good substitute for CRM in AJCC stage I patients. Conclusion: CRM positivity is a strong unfavorable survival indicator for colon cancer patients. A better outcome is expected with CRM values larger than 30 mm. This cutoff value only applied to stage II-IV patients. For stage I patients, number of regional lymph nodes is a good substitute to predict survival. Chemotherapy was another favorable prognostic factor, especially for patients with a CRM value between 0 and 30 mm.

Clinicopathological characteristics and prognosis of colorectal mucinous adenocarcinoma and nonmucinous adenocarcinoma: a surveillance, epidemiology, and end results (SEER) population-based study.

BACKGROUND: Mucinous adenocarcinoma (MC) is a rare histological subtype of colorectal adenocarcinoma. Previous studies investigating the prognosis of MC have conflicting results and the proper treatment of MC remains unclear. METHODS: This retrospective study presents the clinicopathological characteristics and prognosis of MC. This cohort study collected data from April 1 through August 01, 2018. This study used data on 107,735 patients with nonmucinous adenocarcinoma (NMC) and 9,494 with MC between 2009 and 2013 from the Surveillance, Epidemiology, and End Results program (SEER). Clinicopathological features were analyzed by chi-square test and survival curves by the Kaplan-Meier method. We used propensity score matching (PSM) to account for potential bias. Logistic regression and Cox proportional hazards models were used to compare and calculate adjusted risks of MC death. RESULTS: MC was more frequent in patients with older age, large tumor size and moderate tumor grade compared with NMC (P<0.001). Five-year survival was lower for MC patients than NMC patients (P<0.001). Older age, later tumor node metastasis (TNM) stage and multiple tumors indicated a poorer prognosis while surgery gave better survival outcomes [hazard ratio (HR) =0.38; 95% confidence interval (CI), 0.33 to 0.44; P<0.001]. Younger age, left-side colon location and early disease stage were associated with better survival after surgery (P<0.001). CONCLUSIONS: Age, TNM stage, tumor number and treatment were indicators of prognosis and surgery gave better survival for MC patients compared with those without surgery. Our study contributes to their clinical treatment.

Laparoscopic management of cholecystoenteric fistula: A single-center experience.

Aim To report our experience regarding management of cholecystoenteric fistula (CEF) and identify the most effective diagnostic methods and surgical treatment. Methods In total, 10,588 patients underwent laparoscopic cholecystectomy for cholecystolithiasis from January 2000 to December 2014 at the Research Institute of General Surgery, Jinling Hospital (Nanjing, China). Twenty-nine patients were diagnosed with CEF preoperatively or intraoperatively. Data were retrospectively collected on demographics, preoperative diagnostics, intraoperative findings, laparoscopic procedures, complications, and follow-up. Results Twenty-nine patients (female/male ratio, 2.2; mean age, 68.7 years) with CEF were evaluated. Twenty-three (79.3%) patients had a cholecystoduodenal fistula (CDF), four (13.8%) had a cholecystocolonic fistula (CCF), one (3.4%) had a cholecystogastric fistula, and one (3.4%) had a CDF combined with a CCF. Only nine (31.0%) patients obtained a preoperative diagnosis. All patients initially underwent laparoscopic treatment, but five (17.2%) underwent conversion to open surgery; three of these five developed postoperative morbidity or mortality, and the other two had an uneventful postoperative course. Among patients managed successfully by laparoscopy, the hospital stay ranged from 3 to 6 days (mean, 4 days). All patients were asymptomatic at a mean follow-up of 13 months (range, 3-21 months). Conclusion Ultrasound and computed tomography can provide valuable diagnostic clues for CEF. Laparoscopic management of CEF in experienced hands is safe, feasible, and associated with rapid postoperative recovery.

Repeated lung lavage with extracorporeal membrane oxygenation treating severe acute respiratory distress syndrome due to nasogastric tube malposition for enternal nutrition: a case report.

Enternal nutritional support, a frequently applied technique for providing nutrition and energy, played a pivotal role in the treatment of high risk patients. However, severe complications induced by malposition of nasogastric tube caused great danger and even death to the patients. In this case report, we present a patient with severe acute respiratory distress syndrome (ARDS) induced by bronchopleural fistula (BPF) due to malposition of nasogastric tube. Repeated lung lavage combined with extracorporeal membrane oxygenation (ECMO) was performed after transferring to the ICU of our hospital. Finally, the patient recovered and discharged 7 days after admission.