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Introduction Systemic histaminergic activity is elevated in patients with diabetes mellitus. There are a few studies suggesting that histamine is implicated in the pathogenesis of diabetes, but the exact role of histamine in the development of diabetic retinopathy is unclear. The aim of this study was to investigate the role of histamine receptor H4 (HRH4) in the regulation of retinal pigment epithelium (RPE)-derived pro-angiogenic and anti-angiogenic factors under diabetic conditions.Research design and methods The levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), histamine and histidine decarboxylase (HDC) in the serum and vitreous samples of patients with diabetes were compared with those of patients without diabetes. The effect of hyperglycemia on expression levels of HRH4, VEGF, IL-6 and pigment epithelium-derived factor (PEDF) in the RPE was determined. The role of HRH4 in high glucose-induced regulation of VEGF, IL-6 and PEDF in ARPE-19 cells and the underlying regulatory mechanism were verified using an RNA interference-mediated knockdown study.Results The serum and vitreous levels of VEGF, IL-6, histamine and HDC were more increased in patients with diabetic retinopathy than in patients without diabetes. HRH4 was overexpressed in RPE both in vitro and in vivo. Histamine treatment upregulated VEGF and IL-6 and downregulated PEDF expression in ARPE-19 cells cultivated under hyperglycemic conditions. Hyperglycemia-induced phosphorylation of p38 and subsequent upregulation of VEGF and IL-6 and downregulation of PEDF were dampened by small interfering RNA-mediated knockdown of HRH4 in ARPE-19 cells.Conclusions Taken together, HRH4 was a critical regulator of VEGF, IL-6 and PEDF in the RPE under hyperglycemic conditions and the p38 mitogen-activated protein kinase pathway mediated this regulatory mechanism.

For the technical scheme of the two-dimensional trajectory correction projectiles (TDTCPs) with drag brake and despining blade, the mathematical model of two dimensional trajectory corrections is discussed based on the theory of exterior ballistics. An approximate formula for predicting the ballistic drift and trajectory correction quantity is deduced with respect to the process of lateral trajectory correction. The capability of lateral trajectory correction and the flight stability of TDTCP are also analyzed. By comparing with the results of flight test, the accuracy and effectiveness of this approximate calculation method are verified. The result of the approximate method is in accordance with those of 6DOF trajectory model and firing test, and the maximum error is no more than 40 m. All the work is valuable for further research. [ABSTRACT FROM AUTHOR]

Background BRAF mutation has been recognized as an important biomarker of colorectal cancer (CRC) for targeted therapy and prognosis prediction. However, sequencing for every CRC case is not cost-effective. An antibody specific for BRAF V600E mutant protein has been introduced, and we thus examined the utility of BRAF VE1 immunohistochemistry for evaluating BRAF mutations in CRC. Methods Fifty-one BRAF-mutated CRCs and 100 age and sexmatched BRAF wild-type CRCs between 2005 and 2015 were selected from the archives of Asan Medical Center. Tissue microarrays were constructed and stained with BRAF VE1 antibody. Results Forty-nine of the 51 BRAF-mutant CRCs (96.1%) showed more than moderate cytoplasmic staining, except for two weakly stained cases. Six of 100 BRAF wild-type cases also stained positive with BRAF VE1 antibody; four stained weakly and two stained moderately. Normal colonic crypts showed nonspecific weak staining, and a few CRC cases exhibited moderate nuclear reactivity (3 BRAF-mutant and 10 BRAF wild-type cases). BRAF-mutated CRC patients had higher pathologic stages and worse survival than BRAF wild-type patients. Conclusions BRAF VE1 immunohistochemistry showed high sensitivity and specificity, but occasional nonspecific staining in tumor cell nuclei and normal colonic crypts may limit their routine clinical use. Thus, BRAF VE1 immunohistochemistry may be a useful screening tool for BRAF V600E mutation in CRCs, provided that additional sequencing studies can be done to confirm the mutation in BRAF VE1 antibody-positive cases.

Purpose Colostomy creation is an essential procedure for colorectal surgeons, but the preferred method of colostomy varies by surgeon. We compared the outcomes of trephine colostomy creation with open those for the (laparotomy) and laparoscopic methods and evaluated appropriate indications for a trephine colostomy and the advantages of the technique. Methods We retrospectively evaluated 263 patients who had undergone colostomy creation by trephine, open and laparoscopic approaches between April 2006 and March 2016. We compared the clinical features and the operative and postoperative outcomes according to the approach used for stoma creation. Results One hundred sixty-three patients (62%) underwent colostomy surgery for obstructive causes and 100 (38%) for fistulous problems. The mean operative time was significantly shorter with the trephine approach (trephine, 46.0 ± 1.9 minutes; open, 78.7 ± 3.9 minutes; laparoscopic, 63.5 ± 5.0 minutes; P < 0.001), as was the time to flatus (1.8 ± 0.1 days, 2.1 ± 0.1 days, 2.2 ± 0.3 days, P = 0.025). Postoperative complications (

The C‐type lectin‐like domain of CLEC14a (CLEC14a‐C‐type lectin‐like domain [CTLD]) is a key domain that mediates endothelial cell–cell contacts in angiogenesis. However, the role of CLEC14a‐CTLD in pathological angiogenesis has not yet been clearly elucidated. In this study, through complementarity‐determining region grafting, consecutive deglycosylation, and functional isolation, we generated a novel anti‐angiogenic human monoclonal antibody that specifically targets CLEC14a‐CTLD and that shows improved stability and homogeneity relative to the parental antibody. We found that this antibody directly inhibits CLEC14a‐CTLD‐mediated endothelial cell–cell contact and simultaneously downregulates expression of CLEC14a on the surface of endothelial cells. Using various in vitro and in vivo functional assays, we demonstrated that this antibody effectively suppresses vascular endothelial growth factor (VEGF)‐dependent angiogenesis and tumor angiogenesis of SNU182 human hepatocellular carcinoma, CFPAC‐1 human pancreatic cancer, and U87 human glioma cells. Furthermore, we also found that this antibody significantly inhibits tumor angiogenesis of HCT116 and bevacizumab‐adapted HCT116 human colorectal cancer cells. These findings suggest that antibody targeting of CLEC14a‐CTLD has the potential to suppress VEGF‐dependent angiogenesis and tumor angiogenesis and that CLEC14a‐CTLD may be a novel anti‐angiogenic target for VEGF‐dependent angiogenesis and tumor angiogenesis.

Purpose Colorectal cancer (CRC) is generally considered a disease of old age. Most CRCs are diagnosed at age 50 and over. CRC rarely occurs in teenagers, and the clinical features and prognosis of CRC are not clear in this population. The aim of this study was to uncover the clinicopathologic characteristics of teenage sporadic CRC. Methods Of the 21,042 patients who underwent operation for primary CRC at Asan Medical Center between July 1989 and December 2014, 19 cases (0.09%) without a familial history of CRC before 20 years of age at diagnosis were enrolled in this study. The clinicopathologic features of the teenage sporadic CRC patients were retrospectively reviewed. Results Of the 19 patients, 16 patients (84.2%) were male. The most common primary site was the left colon (descending colon & sigmoid colon) in nine patients. With respect to histologic type, adenocarcinoma represented 57.8% of cases, mucinous adenocarcinoma, 31.5%, and signet ring cell carcinoma, 10.5%. Six (31.5%) patients showed peritoneal seeding at presentation. In survival analysis, the 5-year overall survival rate of the patients who underwent curative surgery was 71.3%. Conclusion Teenage sporadic CRC is a very rare disease and the proportion of patients with a poor histologic subtype is high, but early detection and radical treatment can lead to favorable survival rates.

Abstract Background De novo transcriptome assembly is an important technique for understanding gene expression in non-model organisms. Many de novo assemblers using the de Bruijn graph of a set of the RNA sequences rely on in-memory representation of this graph. However, current methods analyse the complete set of read-derived k-mer sequence at once, resulting in the need for computer hardware with large shared memory. Results We introduce a novel approach that clusters k-mers as the first step. The clusters correspond to small sets of gene products, which can be processed quickly to give candidate transcripts. We implement the clustering step using the MapReduce approach for parallelising the analysis of large datasets, which enables the use of compute clusters. The computational task is distributed across the compute system using the industry-standard MPI protocol, and no specialised hardware is required. Using this approach, we have re-implemented the Inchworm module from the widely used Trinity pipeline, and tested the method in the context of the full Trinity pipeline. Validation tests on a range of real datasets show large reductions in the runtime and per-node memory requirements, when making use of a compute cluster. Conclusions Our study shows that MapReduce-based clustering has great potential for distributing challenging sequencing problems, without loss of accuracy. Although we have focussed on the Trinity package, we propose that such clustering is a useful initial step for other assembly pipelines.