miR-888 functions as an oncogene and predicts poor prognosis in colorectal cancer.

MicroRNAs (miRNAs) are important regulators of tumor formation, progression and metastasis. The present study characterized a novel miRNA (miR)-888, as a potent oncomiR in human colorectal cancer (CRC). The clinicopathological investigation on 126 cases of CRC patients demonstrated that the expression level of miR-888 was significantly upregulated in tumors compared with adjacent healthy tissue, and was associated with tumor stage and histological differentiation. A Kaplan-Meier analysis and log-rank test demonstrated that CRC patients with increased miR-888 expression exhibited a decreased overall survival (OS) and disease-free survival (DFS) compared with patients with low miR-888 expression. Further univariate and multivariate analyses identified miR-888 as an independent prognostic factor for poor survival outcome in CRC patients. To determine the biological role of miR-888 in human CRC, in vitro Cell Counting kit-8, wound healing and transwell assays were performed and demonstrated that miR-888 contributed greatly to CRC cell proliferation, invasion and metastasis. Furthermore, potential targets of miR-888 were investigated using a luciferase reporter assay, followed by polymerase chain reaction and western blot analysis. The findings revealed that miR-888 directly bound to the 3'-untranslated region of mothers against decapentaplegic-4 and thus inhibited its expression and promoted the tumor growth factor-1-induced cancer metastasis signaling. The results of the present study identified miR-888 as an oncogenic miRNA in CRC and provide a foundation for promising research in the future regarding this predictive and prognostic biomarker.

MMP16 is a marker of poor prognosis in gastric cancer promoting proliferation and invasion.

Matrix metalloproteinases (MMPs) are closely associated with tumor proliferation, invasion and metastasis. In this study, we determined the MMPs expression and their clinical significances in gastric cancer (GC). We first extensive studied MMPs expression in GC in The Cancer Genome Atlas (TCGA) RNA sequence database and found MMP16 was candidate biomarker in GC. Then we validated clinical significance of MMP16 mRNA expression in 167 GC by RT-PCR. Survival analysis showed that high expression of MMP16 indicated poor overall and disease free survival (P<0.001). The proliferation and invasion potential of GC cells were determined by CCK8, colony formation and Transwell assays. Silencing of MMP16 expression significantly decreased the invasion and proliferation capacity of GC cells (P<0.05). In conclusion, MMP16 was highly expressed and correlated with poor prognosis in GC patients by promoting proliferation and invasion of GC cells. MMP16 could be a novel molecular target and prognostic marker for GC.

Capsule endoscopy in the diagnosis of an exophytic gastrointestinal stromal tumor in the small intestine of a young adult woman: A case report.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that mainly arise in the gastrointestinal tract. They are usually asymptomatic and are incidentally discovered during endoscopy or surgery. Diagnosis is confirmed by histological examination of the specimen. This is the case report of an asymptomatic GIST of the small intestine diagnosed by wireless capsule endoscopy. The tumor was initially suspected to be a leiomyoma, as GISTs in young adults are rare and are mainly discovered incidentally during colorectal cancer screening. The patient was a 35-year-old woman with occult gastrointestinal bleeding, with a normal medical history. An endoscopic assessment of the upper and lower GI tract (gastroscopy and colonoscopy) was performed, but did not reveal any abnormalities. Subsequently, an exophytic tumor initially suspected as leiomyoma or external pressure was detected in the small intestine by capsule endoscopy. A computed tomography scan was suggestive of a soft tissue tumor arising from the small intestine. A surgical specimen was obtained and the immunohistochemical examination revealed that the tumor was positive for CD117 and discovered on GIST-1 markers, while the markers of carcinoma, melanoma and lymphoma were negative, which was consistent with a diagnosis of a low-risk GIST with a mitotic count of <5/50 high-power fields. In this study, we aimed to present in detail the capsule endoscopic and radiological characteristics, as well as the findings of the histological examination of the surgical specimen. In conclusion, when occult blood is detected in the stool, even when gastroscopy and colonoscopy reveal no abnormal findings, small intestinal lesions should be suspected. Exophytic small intestinal GISTs, although rare, particularly in younger patients, they should be considered by physicians in the differential diagnosis of obscure GI bleeding of unknown origin, in order to reduce morbidity and mortality. Capsule endoscopy may be considered to be the first choice as a diagnostic tool for obscure GI bleeding.

Carbon dioxide insufflation or warm-water infusion for unsedated colonoscopy: A randomized controlled trial in patients with chronic constipation in China.

AIMS: The effect of carbon dioxide (CO2) insufflation and warm-water infusion during colonoscopy on patients with chronic constipation remains unknown. We evaluated CO 2 insufflation and warm-water irrigation versus air insufflation in unsedated patients with chronic constipation in China. PATIENTS AND METHODS: This randomized, single-center, controlled trial enrolled 287 consecutive patients, from January 2014 to January 2015, who underwent colonoscopy for chronic constipation. Patients were randomized to CO2 insufflation, warm-water irrigation and air insufflation colonoscopy insertion phase groups. Pain scores were assessed by the visual analog scale (VAS). The primary outcome was real-time maximum insertion pain, recorded by an unblinded nurse assistant. At discharge, the recalled maximum insertion pain was recorded. Meanwhile, patients were requested to select the VAS at 0, 10, 30, and 60 min after the procedure. In addition, cecal intubation and withdrawal time, total procedure time, and adjunct measures were recorded. RESULTS: A total of 287 patients were randomized. The correlation between real-time and recalled maximum insertion pain ((Pearson coefficient r = 0.929; P < 0.0001) confirmed internal validation of the primary outcome. The mean real-time maximum pain scores during insertion 2.9 ± 2.1 for CO2, 2.7 ± 1.9 for water achieved a significantly lower pain score compared with air (5.7 ± 2.5) group (air vs CO2 P < 0.001; air vs water P < 0.001). However, no significant pain score differences were found between the patients in the CO2 and water groups (CO2 vs water, P = 0.0535). P values in painless colonoscopy and only discomfort colonoscopy (pain 1-2) were, respectively, 6 (6.4%) and 8 (8.5%) for air; 17 (17.7%) and 29 (30.2%) for CO2; 16 (16.5%) and 31 (31.9%) for water. At 0, 10, 30, and 60 min postprocedure, pain scores showed in the CO2 and water groups had significantly reduced than in air group. Insertion time was significantly different between air (10.6 ± 2.5) and CO2 ( 7.2 ± 1.4) (air vs CO2 P < 0.001), air and water (6.9 ± 1.3) (air vs water P < 0.001). However, CO2 and was not significantly different in cecum-intubated time (CO2 vs water, P = 0.404). CO2 and water group in extubation time were significantly different, respectively, CO2 (7.9 ± 1.1) and water (8.0 ± 1.1) (CO2 vs water, P = 0.707). CO2 or water group required less implementation of adjunct measures and more willingness to repeat the procedure. CONCLUSIONS: Compared with air, the CO2 or water-aided method reduced real-time maximum pain and cecum-intubated time for chronic constipated patients in unsedated colonoscopy. The CO2 insufflation or warm-water irrigation may be a simple and inexpensive way to reduce discomfort in unsedated patients with constipation. This study demonstrated an advantage of using CO2 insufflation and warm-water irrigation during colonoscopy in unsedated constipated patients in China.

Interleukin-18 genetic polymorphisms contribute differentially to the susceptibility to Crohn's disease.

AIM: To investigate the correlation between interleukin-18 (IL-18) gene polymorphisms and the risk of developing Crohn's disease (CD). METHODS: The PubMed, CISCOM, CINAHL, Web of Science, EBSCO, Cochrane Library, MEDLINE, EMBASE and CBM databases were searched without any language restrictions using combinations of keywords relating to CD and IL-18 for relevant articles published before November 1(st), 2013. Screening of the published studies retrieved from searches was based on our stringent inclusion and exclusion criteria and resulted in seven eligible studies for meta-analysis. A meta-analysis was conducted using a random-effects model with STATA 12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (95%CI) were calculated. RESULTS: Seven case-control studies, with a total of 1930 CD cases and 1930 healthy subjects, met our inclusion criteria. The results of our meta-analysis indicated that the IL-18 rs1946518 A>C and rs187238 G>C polymorphisms may correlate with an increased risk of CD under five genetic models (all P < 0.05). Furthermore, we observed positive associations between the IL-18 rs360718 A>C polymorphism and CD risk under three genetic models (C allele vs A allele: OR = 2.03, 95%CI: 1.20-3.43, P = 0.008; CC vs AA+AC: OR = 2.39, 95%CI: 1.2-4.43, P = 0.006; CC vs AC: OR = 2.31, 95%CI: 1.22-4.38, P = 0.010). However, such associations were not found for the IL-18 rs917997 C>T, codon 35 A>C and rs1946519 G>T polymorphisms (all P > 0.05). A subgroup analysis was conducted to investigate the effect of ethnicity on an individual's susceptibility to CD. Our results revealed positive correlations between IL-18 genetic polymorphisms and an increased risk of CD among Asians and Africans (all P < 0.05), but not among Caucasians (all P > 0.05). CONCLUSION: This meta-analysis indicated that the IL-18 rs1946518 A>C, rs187238 G>C and rs360718 A>C polymorphisms may contribute to susceptibility to CD, especially among Asians and Africans. These polymorphisms are known to reduce IL-18 mRNA and protein levels.

Suppression effects of negative pressure on the proliferation and metastasis in human pancreatic cancer cells.

BACKGROUND AND AIMS: The aim was to explore the effect of negative pressure on the proliferation and metastasis of human pancreatic cancer SW1990 cells. SETTINGS AND DESIGN: Three groups were conducted in the work: normal control group (NC group, 0 mm Hg), low negative pressure group (LN group, -300 mm Hg), and high negative pressure group (HN group, -600 mm Hg). MATERIALS AND METHODS: Cell morphological assay was conducted using an inverted Nikon TE2000-S microscope. Cell viability was assayed using cell counting kit-8 solution. Cell apoptosis was evaluated with flow cytometry. Cell migration was investigated using transwell assay. RESULTS: Compared to LN and HN groups, SW1990 cells in NC group grew quite well, showing a higher density. The NC group represented the highest cell viability. The HN group represented the lowest cell viability, which was lower than that of the LN group (P < 0.01). The apoptosis rate in NC group, LN group and HN group was 1.91% ± 0.13%, 2.31% ± 0.06% and 15.22% ± 0.81%, respectively (P < 0.05). The average number of migration cells in NC group was 53.60 ± 4.14 (× 200), which was decreased to 18.93 ± 3.67 and 11.07 ± 3.01 in LN group and HN group, respectively (P < 0.01). CONCLUSION: The negative pressure shows suppression effects on the proliferation and metastasis of human pancreatic cancer SW1990 cells. It is indicated that negative pressure may be involved in the development of human pancreatic cancer by influencing cell biological characteristics.

Prognostic impact of gastrointestinal bleeding and expression of PTEN and Ki-67 on primary gastrointestinal stromal tumors.

BACKGROUND: Prognostic indicators for gastrointestinal stromal tumors (GISTs) are under investigation. The latest risk classification criteria may still have room for improvement. This study aims to investigate prognostic factors for primary GISTs from three aspects, including clinicopathological parameters, immunohistochemical (IHC) expression of PTEN, and Ki-67 labeling index (LI), and attempts to find valuable predictors for the malignancy potential of primary GISTs. METHODS: Tumor samples and clinicopathological data from 84 patients with primary GISTs after R0 resection were obtained. Immunohistochemical analysis was performed based on tissue microarray (TMA) to estimate expression of PTEN and Ki-67 in tumor cells. RESULTS: The cut-off point of Ki-67 LI was determined as 1%, using a receiver operator characteristic test with a sensitivity of 71.7% and a specificity of 64.5%. Univariate analysis demonstrated the following factors as poor prognostic indicators for relapse-free survival (RFS) against a median follow-up of 40.25 months: gastrointestinal (GI) bleeding (P = 0.009), non-gastric tumor location (P = 0.001), large tumor size (P = 0.022), high mitotic index (P < 0.001), high cellularity (P = 0.012), tumor rupture (P = 0.013), absent or low expression of PTEN (P = 0.036), and Ki-67 LI >1% (P = 0.043). Gastrointestinal bleeding (hazard ratio, 3.85; 95% confidence interval, 1.63 to 9.10; P = 0.002) was a negative independent risk predictor in multivariate analysis, in addition to tumor size (P = 0.023), and mitotic index (P = 0.002). In addition, GI bleeding showed a good ability to predict recurrence potential, when included in our re-modified risk stratification criteria. CONCLUSIONS: This study suggests that GI bleeding is an independent predictor of poor prognosis for RFS in primary GISTs. Expression of PTEN and Ki-67 are correlated with high risk potential and may predict early recurrence in univariate analysis.

Gastrointestinal symptom due to lupus peritonitis: a rare form of onset of SLE.

Serositis is commonly seen in systemic lupus erythematosus (SLE). Approximately 16% of patients with SLE have pleural or pericardial involvement. However, peritoneal involvement is extremely rare, and SLE with ascites as the first manifestation is an even rarer condition. This is the case report of a 19-year old male with discoid lupus who evolved with gastrointestinal symptoms as the first manifestation of the disease, characterized by significant abdominal distension and pain, asthenia, vomiting, and signs of ascites. An abdominal CT scan demonstrated ascites and marked edematous thickening of the bowel wall, which appeared as "target sign", and "double-track sign". Laboratory tests showed that his serum complement levels decreased and that he was positive for anti-nRNP/Sm antibodies, anti-Sm antibodies, anti-SS-A antibody, and anti-nuclear antibodies. The patient was treated with prednisone and chloroquine, with substantial improvement of his condition.

Serum inter-cellular adhesion molecule 1 is an early marker of diagnosis and prediction of severe acute pancreatitis.

AIM: To determine if serum inter-cellular adhesion molecule 1 (ICAM-1) is an early marker of the diagnosis and prediction of severe acute pancreatitis (SAP) within 24 h of onset of pain, and to compare the sensitivity, specificity and prognostic value of this test with those of acute physiology and chronic health evaluation (APACHE) II score and interleukin-6 (IL-6). METHODS: Patients with acute pancreatitis (AP) were divided into two groups according to the Ranson's criteria: mild acute pancreatitis (MAP) group and SAP group. Serum ICAM-1, APACHE II and IL-6 levels were detected in all the patients. The sensitivity, specificity and prognostic value of the ICAM-1, APACHE II score and IL-6 were evaluated. RESULTS: The ICAM-1 level in 36 patients with SAP within 24 h of onset of pain was increased and was significantly higher than that in the 50 patients with MAP and the 15 healthy volunteers (P < 0.01). The ICAM-1 level (25 ng/mL) was chosen as the optimum cutoff to distinguish SAP from MAP, and the sensitivity, specificity, positive predictive value, negative predictive value (NPV), positive likelihood ratio and negative likelihood ratio were 61.11%, 71.42%, 0.6111, 0.7142, 2.1382 and 0.5445, respectively. The area under the curve demonstrated that the prognostic accuracy of ICAM-1 (0.712) was similar to the APACHE-II scoring system (0.770) and superior to IL-6 (0.508) in distinguishing SAP from MAP. CONCLUSION: ICAM-1 test is a simple, rapid and reliable method in clinical practice. It is an early marker of diagnosis and prediction of SAP within the first 24 h after onset of pain or on admission. As it has a relatively low NPV and does not allow it to be a stand-alone test for the diagnosis of AP, other conventional diagnostic tests are required.

Clinical observations on 46 cases of globus hystericus treated with modified Banxia Houpu decoction.

OBJECTIVE: To observe the therapeutic effect and mechanism of modified Banxia Houpu decoction on globus hystericus. METHODS: The 95 patients with globus hystericus were randomly divided into a treatment group of 46 cases treated with modified Banxia Houpu decoction and a control group of 49 cases treated with Manyanshuning (Granula for Clearing the Throat). In addition, a normal group of 24 healthy people was set up. SCL-90 scale was adopted to observe the therapeutic effect, evaluate the psychological state of patients and build a database on combination of four diagnoses. RESULTS: The effect of the modified Banxia Houpo decoction was better than that of the control group in relieving depression, anxiety and improving the psychological state (P<0.05 or P<0.01). CONCLUSION: Modified Banxia Houpu decoction has definite therapeutic effect on globus hystericus. Its mechanism may be related to its function in relieving depression and anxiety and regulating the psychological state.

[Inhibitory effects of Scutellaria barbatae D. Don on tumor angiogenesis and its mechanism].

BACKGROUND & OBJECTIVE: Various chemically synthetic anti-angiogenesis agents have serious side effects. The traditional Chinese medicine has attracted considerable attention because of its low toxicity. This study was to explore the inhibitory effects of Scutellaria barbatae D. Don, a kind of traditional Chinese medicinal anti-cancer herb, on tumor angiogenesis, and investigate its mechanism. METHODS: Matrigel plug and human umbilical vascular endothelial cells (HUVECs) were used to construct in vivo and in vitro models of angiogenesis to assess the effect of Scutellaria barbatae D. Don on angiogenesis. After cultured with Scutellaria barbatae D. Don, the migration of endothelial cells was examined by Transwell chamber; the expression of vascular endothelial growth factor (VEGF) in HeLa cells was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Scutellaria barbatae D. Don significantly inhibited angiogenesis in Matrigel; the tube formation number was significantly lower in 20% and 40% medicated serum groups containing Scutellaria barbatae D. Don than in 20% and 40% drug-free serum groups (5.6+/-1.1 vs. 9.8+/-1.3, P=0.001; 1.0+/-0.7 vs. 13.4+/-1.1, P<0.001). Migrated endothelial cells was significantly fewer in 20% and 40% medicated serum groups containing Scutellaria barbatae D. Don than in 20% and 40% drug-free serum groups (19.75+/-2.63 vs. 24.25+/-2.06, P=0.038; 14.00+/-2.58 vs. 26.5+/-4.65, P=0.006). When treated for 24 h and 48 h, the expression of VEGF in HeLa cells was significantly lower in 40% medicated serum group containing Scutellaria barbatae D. Don than in 40% drug-free serum group (138.67+/-9.50 vs. 195.82+/-2.43, P=0.006; 93.84+/-41.11 vs. 193.68+/-18.37, P=0.036). CONCLUSION: Scutellaria barbatae D. Don could efficiently inhibit angiogenesis in tumor tissue which might relate with inhibition of endothelial cell migration and down-regulation of VEGF in tumor cells.

Abnormal function of platelets and role of angelica sinensis in patients with ulcerative colitis.

AIM: To explore the abnormal function of platelets and the role of angelica sinensis injection (ASI) in patients with ulcerative colitis (UC). METHODS: In 39 patients with active UC, 25 patients with remissive UC and 30 healthy people, alpha-granule membrane protein (GMP-140) and thromboxane B(2) (TXB(2)) were detected by means of ELISA, 6-keto-PGF(1a) was detected by radioimmunoassay, platelet count (PC) and 1 min platelet aggregation rate (1 min PAR) were detected by blood automatic tester and platelet aggregation tester respectively, and von Willebrand factor related antigen (vWF:Ag) was detected by the means of monoclonal -ELISA. The 64 patients with UC were divided into two therapy groups. After routine treatment and angelica sinensis injection (ASI) + routine treatment respectively for 3 weeks, all these parameters were also detected. RESULTS: The PC, 1 min PAR and levels of GMP-140, TXB(2), and vWF:Ag in active UC were significantly higher than those in remissive UC and normal controls (P<0.05-0.01).Meanwhile, 1 min PAR and levels of GMP-140, TXB(2), and vWF:Ag in remissive UC were still significantly higher than those in normal controls (P<0.05). Furthermore, 6-keto-PGF(1a) level in active and remissive UC was remarkably lower than that in normal control (P<0.05-0.01). These parameters except 6-keto-PGF(1a) were significantly improved after the treatment in ASI therapy group (P<0.05-0.01), whereas they all were little changed in routine therapy group (P>0.05). CONCLUSION: Platelets can be significantly activated in UC, which might be related with vascular endothelium injury and imbalance between TXB(2) and 6-keto-PGF(1a) in blood. ASI can significantly inhibit platelet activation, relieve vascular endothelial cell injury, and improve microcirculation in UC.