Chromoendoscopy with targeted biopsies is superior to white-light endoscopy for the long-term follow-up detection of dysplasia in ulcerative colitis patients: a multicenter randomized-controlled trial.

BACKGROUND: Data from single-center experience or small sample-sized studies have shown that chromoendoscopy (CE) might be superior to white-light endoscopy (WLE) for dysplasia surveillance in ulcerative colitis (UC) patients. We performed a prospective randomized trial with a long-term follow-up to compare the detection rate of dysplasia among WLE with targeted biopsies (WLT), WLE with random biopsies (WLR), and dye-based CE with targeted biopsies (CET) in UC patients. METHODS: Patients with long-standing UC were enrolled from 11 medical centers from March 2012 to December 2013 and randomized into three arms (WLT, WLR, and CET). Only high-definition endoscopy was used in all three groups. The patients were followed up by annual endoscopy with biopsies through December 2017. RESULTS: With a median follow-up time of 55 months, a total of 122 patients with 447 colonoscopies were finally analysed in the per-protocol set: WLT (n = 43), WLR (n = 40), and CET (n = 39). A total of 34 dysplastic lesions were found in 29 colonoscopies of 21 patients. WLR and CET could identify more colonoscopies that diagnosed dysplasia than WLT (8.1% and 9.7% vs 1.9%; P = 0.014 and 0.004, respectively). WLR obtained more biopsied samples than WLT and CET (16.4 ± 5.1 vs 4.3 ± 1.4 and 4.3 ± 1.4; both P < 0.001). During the second half of the follow-up (37 - 69 months), CET could identify more colonoscopies that diagnosed dysplasia than WLT (13.3% vs 1.6%, P = 0.015) and showed a trend for increasing the detection rate compared with WLR (13.3% vs 4.9%, P = 0.107). CONCLUSIONS: For a better outcome of cancer/dysplasia surveillance in patients with long-standing UC, CET appeared to be more effective than WLT and less tedious than WLR. CET was found to be particularly useful when a long-term (>3 years) follow-up was conducted for dysplasia surveillance. The trial was registered on www.chictr.org.cn (ChiCTR1900023689).

Multimodality Imaging of Angiogenesis in a Rabbit Atherosclerotic Model by GEBP11 Peptide Targeted Nanoparticles.

Background and Aims: Angiogenesis is an important pathological process during progression of plaque formation, which can result in plaque hemorrhage and vulnerability. This study aims to explore non-invasive imaging of angiogenesis in atherosclerotic plaque through magnetic resonance imaging (MRI) and positron emission tomography (PET) by using GEBP11 peptide targeted magnetic iron oxide nanoparticles in a rabbit model of atherosclerosis. Methods: The dual-modality imaging probe was constructed by coupling 2, 3-dimercaptosuccinnic acid-coated paramagnetic nanoparticles (DMSA-MNPs) and the PET 68Ga chelator 1,4,7-triazacyclononane-N, N', N''-triacetic acid (NOTA) to GEBP11 peptide. The atherosclerosis model was induced in New Zealand white rabbits by abdominal aorta balloon de-endothelialization and atherogenic diet for 12 weeks. The plaque areas in abdominal artery were detected by ultrasound imaging and Oil Red O staining. Immunofluorescence staining and Prussian blue staining were applied respectively to investigate the affinity of GEBP11 peptide. MTT and flow cytometric analysis were performed to detect the effects of NGD-MNPs on cell proliferation, cell cycle and apoptosis in Human umbilical vein endothelial cells (HUVECs). In vivo MRI and PET imaging of atherosclerotic plaque were carried out at different time points after intravenous injection of nanoparticles. Results: The NGD-MNPs with hydrodynamic diameter of 130.8 nm ± 7.1 nm exhibited good imaging properties, high stability, low immunogenicity and little cytotoxicity. In vivo PET/MR imaging revealed that 68Ga-NGD-MNPs were successfully applied to visualize atherosclerotic plaque angiogenesis in the rabbit abdominal aorta. Prussian blue and CD31 immunohistochemical staining confirmed that NGD-MNPs were well co-localized within the blood vessels' plaques. Conclusion:68Ga-NGD-MNPs might be a promising MR and PET dual imaging probe for visualizing the vulnerable plaques.

Population-specific genome-wide mapping of expression quantitative trait loci in the colon of Han Chinese.

OBJECTIVE: To establish the colonic expression quantitative trait locus map in Han Chinese population and provide a functional reference for interpreting genetic associations of diseases such as inflammatory bowel disease (IBD). METHODS: Colonic mucosal biopsies and peripheral blood samples were obtained from 48 Chinese Han individuals (24 ulcerative colitis patients and 24 healthy controls). Transcription profiling was performed using human whole genome expression array. Genotyping was done using a population-specific genotype array. Imputation was performed using IMPUTE2. Association between genotypes and gene expression was analyzed using a Matrix Expression Quantitative Trait Loci (eQTL) R package to identify eQTL. We used ChIPpeakAnno R package for annotation of the eQTL. Linkage disequilibrium between the eQTL and IBD risk loci was also investigated. RESULTS: We identified 6 377 single nucleotide polymorphism-transcript interactions (cis-eQTL) in the colon of the Chinese participants. Most of the eQTL located near the transcription starting sites and overlapped with histone modification marks on the genome. A significant proportion of the eQTL were found to be within transcription factor-binding sites. Two IBD risk loci were found to be colon cis-eQTL in Chinese individuals, and 51 cis-eQTL were identified in another 18 IBD risk loci. CONCLUSIONS: This study defined a population-specific catalogue of colon eQTL in the Chinese population. Potential functional variants of IBD association signals were identified. We provided a useful reference dataset for fine mapping IBD risk loci and identifying causal variants in the Chinese Han population.

Increased expression of HSP27 inhibits invasion and metastasis in human esophageal squamous cell carcinoma.

Previous studies have indicated that heat shock protein 27 (HSP27) had high correlation with the development and progression in several tumors. However, the roles of HSP27 in esophageal squamous cell carcinoma (ESCC) were uncertain. The aim in this study is to investigate the potential roles of HSP27 in the metastasis of ESCC. The expression of HSP27 in ESCC tissues and four human esophageal cancer cell lines were examined by immunohistochemistry and Western blotting, respectively. Wound healing assays, transwell assays, and in vivo assays were used to identify the differences of metastasis potential between normal and HSP27 overexpressed cells. HSP27 expression was downregulated in cancer tissue compared to the matched normal tissue. And the positive staining was mainly located in the cytoplasm. Statistical analyses showed that the expression of HSP27 in ESCC was significantly correlated with the tumor differentiation (P = 0.023), the patient's TNM stage (P = 0.013), lymph metastasis (P = 0.020), and distant metastasis (P = 0.017). HSP27 expression was significantly lower in highly metastatic cells than the less ones. The metastatic potentials of EC9706-H and EC109-H cells were higher than EC9706-L and EC109-L cells. In vitro and in vivo assays showed that overexpression of HSP27 in highly metastatic cells dramatically decreased their metastatic capacity. This study indicated that the expression level of HSP27 may be inversely correlated with the metastasis behavior of ESCC, and HSP27 may play an important role in this progression. HSP27 may be a potential molecular target for the therapy and prognosis of patients with ESCC.

Increased expression of FOXQ1 is a prognostic marker for patients with gastric cancer.

Altered expression of forkhead box Q1 (FOXQ1) is observed in various types of human cancers. However, the clinical significance of FOXQ1 expression in gastric cancer (GC) remains largely unknown. The present study aims to explore the clinicopathological significance and prognostic value of FOXQ1 in GC. FOXQ1 messenger RNA (mRNA) and protein expression were determined by quantitative real-time reverse transcriptase-polymerase chain reaction and Western blot in 20 pairs of fresh frozen GC tissues and corresponding noncancerous tissues. Additionally, FOXQ1 expression was analyzed by immunohistochemistry in 158 clinicopathologically characterized GC cases. The correlation of FOXQ1 expression with patients' survival rate was assessed by Kaplan-Meier and Cox regression. Our results showed that the expression levels of FOXQ1 mRNA and protein in GC tissues were both significantly higher than those in non-cancerous tissues. Our results showed that the high expression of FOXQ1 in GC was related to tumor size (P = 0.026), histological grade (P = 0.021), lymph node involvement (P = 0.002), and tumor-node-metastasis stage (P = 0.028). Kaplan-Meier survival analysis showed that a high expression level of FOXQ1 resulted in a significantly poor prognosis of GC patients. Furthermore, Cox multivariates analysis indicated that FOXQ1 expression level was an independent prognostic factor for the overall survival rate of GC patients. In conclusion, overexpression of FOXQ1 is closely related to progression of GC and might be regarded as an independent predictor of poor prognosis for GC.

Inhibiting gastric cancer-associated angiogenesis by CIAPIN1 siRNA.

Angiogenesis plays an essential role in tumor growth and metastasis and is a promising target for cancer therapy. We characterized the effects of selective CIAPIN1 inhibition on the angiogenesis gastric cancer cell line SGC7901 by stable transfection of CIAPIN1 siRNA. Our study has been shown that CIAPIN1 play the determined role in tumor growth and multidrug resistance. The conditioned media obtained from SGC7901 treated with CIAPIN1 siRNA suppressed in vitro the proliferation, migration and tube formation of human umbilical vein endothelial cells compared with untransfected cells or cells transfected with control vector alone. Furthermore, the stable transfection of CIAPIN1 siRNA inhibited in vivo tumorigenicity and angiogenesis. Our findings support that selective inhibition of CIAPIN1 alone plays an instrumental role on gastric cancer associated angiogenesis.

The analysis of injured and poisoned patients during the construction of urbanization and industrialization from 1998 to 2002.

OBJECTIVE: To analyze the causes of injury and poisoning during construction of urbanization and industrialization and to explore proper measures. METHODS: The data of the patients with injury and poisoning during construction of urbanization and industrialization treated in out hospital from 1998 to 2002 were retrospectively analyzed. RESULTS: The number of discharged patients of injury and poisoning accounted for 29.2% of the total number (49800) of discharged patients in the corresponding period in our hospital, which was greater than that of other city and county hospitals, and accounted for 94.3% of the total number (15,411) of discharged patients of the Surgery Department in the corresponding period in our hospital. Injuries caused by motor vehicle traffic accidents, cutting and piercing instruments or objects, homicide and injury purposely inflicted by other persons and accidental falls held 78.9%. The number of the inpatients in 2002 increased by 83.3% compared with that of 1998, the number of injured and poisoned inpatients increased by 76.1% and these patients aged mainly at age of 15-39 years, holding 80.1%. In a year, the peak period of trauma patients was in summer because of hot weather; the fewest in February for the floating people went home for Spring Festival holidays. CONCLUSIONS: During construction of rural urbanization and industrialization, injuries and poisoning increase evidently and are the main tasks of surgical management. So to raise its treatment level and therapeutic effect is a key point.

Characterization of a specific phage-displayed Peptide binding to vasculature of human gastric cancer.

Antivascular therapy provides a promising method for anticancer therapy. But targeting to gastric cancer vessels is nonselective due in part to the lack of specific cell-surface receptors identified on target vascular cells. Herein we used in vivo screening of phage displayed peptide library to identify some peptides that bind selectively to endothelial cells of human gastric cancer rather than nonendothelial cells. After four rounds of selection, one phage was obtained with a cyclic 7-mer peptide CGNSNPKSC homing to human gastric adenocarcinoma . There was a 4.6 approximately 137.26-fold increase in the number of the selected phage in gastric cancer xenograft in comparision with control organs brain, heart, liver, spleen and kidney. Immunohistochemistry in mouse and human tissue showed that this phage peptide only bind to the endothelial cells of human gastric cancer. This peptide was observed only specific binding to HUVEC not to SGC-7901, Eca-109, LoVo and Hep-G2 by ELISA. The competitive and inhibitory result between the synthetic CGNSNPKSC peptide and the phage displaying the peptide CGNSNPKSC on HUVEC and in vivo was also confirmed its specific binding effect. This peptide may be a possible candidate for targeted drug delivery in antivascular therapy.