Diagnostic value of contrast-enhanced harmonic endoscopic ultrasonography in predicting the malignancy potential of submucosal tumors: a systematic review and meta-analysis.

OBJECTIVES: Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) utilizes the second-harmonic signals from contrast microbubbles located in the vessels to improve the detectability of microcirculation. Many studies have used CH-EUS to stratify the malignancy risk of submucosal tumors (SMTs), discriminate gastrointestinal stromal tumors (GISTs) from benign SMTs, and predict the malignancy of GISTs based on the regularity of vessels or enhancing patterns. The aim of this study was to conduct a meta-analysis to evaluate the diagnostic performance of CH-EUS in the differential diagnosis of SMTs. METHODS: After searching the Medline, Embase, and Cochrane databases systematically, studies that evaluated the diagnostic accuracy of CH-EUS for the prediction of the malignancy potential of SMTs were pooled. The diagnostic accuracy was computed using a stochastic effect model. The overall test performance was summarized with the summary receiver operating characteristic curve. RESULTS: Six studies discriminated GISTs from benign lesions, and three studies discriminated low-risk from high-risk GISTs, covering a total of 354 cases of SMT. The overall accuracy of CH-EUS in predicting malignancy risk can be assessed as follows: sensitivity 0.87 (95% CI 0.82-0.91), specificity 0.82 (95% CI 0.74-0.89), positive likelihood ratio of 3.55 (95% CI 2.39-5.27), negative likelihood ratio of 0.21 (95% CI 0.13-0.33), and diagnostic odds ratio of 22.17 (95% CI 10.43-47.10). The overall area under the curve was 0.89. Subgroup analysis of the sensitivity and specificity for studies discriminating low-risk from high-risk GISTs were 0.93 (95% CI 0.77-0.99) and 0.81 (95% CI 0.63-0.93), respectively. There was evidence of significant heterogeneity, but no proof of publication bias. CONCLUSIONS: CH-EUS is an effective tool for improving the diagnostic accuracy of conventional EUS for discriminating SMTs and is superior to other imaging techniques. However, due to the limited number of well-designed control studies, we should take into consideration the uncertainty of this method when altering a treatment plan.

Rapamycin enhances the anti-angiogenesis and anti-proliferation ability of YM155 in oral squamous cell carcinoma.

YM155, a small molecule inhibitor of survivin, has been studied in many tumors. It has been shown that YM155 inhibited oral squamous cell carcinoma through promoting apoptosis and autophagy and inhibiting proliferation. It was found that YM155 also inhibited the oral squamous cell carcinoma-mediated angiogenesis through the inactivation of the mammalian target of rapamycin pathway. Rapamycin, a mammalian target of rapamycin inhibitor, played an important role in the proliferation and angiogenesis of oral squamous cell carcinoma cell lines. In our study, cell proliferation assay, transwell assay, tube formation assay, and western blot assay were used to investigate the synergistic effect of rapamycin on YM155 in oral squamous cell carcinoma. Either in vitro or in vivo, rapamycin and YM155 exerted a synergistic effect on the inhibition of survivin and vascular endothelial growth factor through mammalian target of rapamycin pathway. Overall, our results revealed that low-dose rapamycin strongly promoted the sensitivity of oral squamous cell carcinoma cell lines to YM155.

Long non-coding RNA UCA1 contributes to the progression of oral squamous cell carcinoma by regulating the WNT/ß-catenin signaling pathway.

With the development of functional genomics studies, a mass of long non-coding RNAs (LncRNA) were discovered from the human genome. Long non-coding RNAs serve as pivotal regulators of genes that are able to generate LncRNA-binding protein complexes to modulate a great number of genes. Recently, the LncRNA urothelial carcinoma-associated 1 (UCA1) has been revealed to be dysregulated, which plays a critical role in the development of a few cancers. However, the role of the biology and clinical significance of UCA1 in the tumorigenesis of oral squamous cell carcinoma (OSCC) remain unknown. We found that UCA1 expression levels were upregulated aberrantly in tongue squamous cell carcinoma tissues and associated with lymph node metastasis and TNM stage. We explored the expression, function, and molecular mechanism of LncRNA UCA1 in OSCC. In the present work, we revealed that UCA1 silencing suppressed proliferation and metastasis and induced apoptosis of OSCC cell lines in vitro and in vivo, which might be related to the activation level of the WNT/ß-catenin signaling pathway. Our research results emphasize the pivotal role of UCA1 in the oncogenesis of OSCC and reveal a novel LncRNA UCA1-ß-catenin-WNT signaling pathway regulatory network that could contribute to our understanding in the pathogenesis of OSCC and assist in the discovery of a viable LncRNA-directed diagnostic and therapeutic strategy for this fatal disease.

The Association of Maternal Body Composition and Dietary Intake with the Risk of Gestational Diabetes Mellitus during the Second Trimester in a Cohort of Chinese Pregnant Women.

OBJECTIVE: To investigate the association of maternal body composition and dietary intake with the risk of gestational diabetes mellitus (GDM). METHODS: A total 154 GDM subjects and 981 controls were enrolled in a prospective cohort study in 11 hospitals from May 20, 2012 to December 31, 2013. Bioelectrical impedance analysis and dietary surveys were used to determine body composition and to evaluate the intake of nutrients in subjects at 21-24 weeks' gestation (WG). Logistic regression analysis was applied to explore the relationships of maternal body composition and dietary intake with the risk of GDM morbidity. RESULTS: Age, pre-pregnant body weight (BW), and body mass index (BMI) were associated with increased risk of GDM. Fat mass (FM), fat mass percentage (FMP), extracellular water (ECW), BMI, BW, energy, protein, fat, and carbohydrates at 21-24 WG were associated with an increased risk of GDM. In contrast, fat free mass (FFM), muscular mass (MM), and intracellular water (ICW) were associated with a decreased risk of GDM. CONCLUSION: Maternal body composition and dietary intake during the second trimester of pregnancy were associated with the risk of GDM morbidity.

Interventional reperfusion for acute embolism of the middle cerebral artery trunk with contralateral internal carotid artery congenital absence.

Internal carotid artery congenital absence with acute embolism of the middle cerebral artery trunk is very rare. A 65-year-old female with a history of hypertension and atrial fibrillation was admitted to the neurology department of our hospital. Computed tomography of the head and neck showed no carotid canal of the petrous portion of the temporal bone; digital subtraction angiography (DSA) showed no left internal carotid artery and the right middle cerebral artery trunk occlusion. These results suggested acute embolism of the middle cerebral artery trunk with contralateral internal carotid artery congenital absence. Mechanical thrombectomy was performed, which had a good outcome. This case showed the vascular anatomy features of ICA congenital absence with contralateral large vessel acute occlusion, and it is essential to promptly identify the vascular variation during the interventional procedure.

CpG oligodeoxynucleotides discriminately enhance binding capacity of human naïve B cells to Hepatitis B virus epitopes.

CpG oligodeoxynucleotides (CpG ODN) have the potential to enhance the antigen-presenting cells function of human naïve B cells. In this study, we aim to define the effect of CpG ODNs on the binding capacity of human naïve B cells for different Hepatitis B virus (HBV) epitopes. Three HLA-A2 restricted epitopes were selected to incubate with CpG ODN-primed human naïve B cells. Binding capacity for each epitope and expression of CD80, CD86, class I major histocompatibility complex (MHC), and class II MHC of naïve B cells was tested, respectively, by flow cytometry. CpG ODNs, especially ODN 2216, enhanced the binding capacity of human naïve B cells for HBV epitopes (p < 0.01), and induced markedly higher expression of CD80, CD86, class I MHC, and class II MHC. The binding capacity of CpG-treated naive B cells for each epitope was significantly different. In all the 3 subjects, CpG ODN 2216-primed naïve B cells showed the highest binding ability for Env172-180 compared with the other epitopes with a high expression of co-stimulatory and MHC molecules. CpG ODN showed the potential to selectively enhance the binding capacity of human naïve B cells for HBV epitopes. These results suggest new strategies for development of vaccine design.

Focal intramural hematoma as a potential pitfall for iatrogenic aortic dissection during subclavian artery stenting: A case report.

BACKGROUND: Iatrogenic aortic dissection (IAD) is a rare but fatal complication of interventional treatment for the proximal supra-aortic large vessels. Several cases of IAD after endovascular treatment of subclavian artery have been reported. Nevertheless, the pathogenesis of IAD is still unclear. Here we report a patient with IAD following a balloon expandable stent implanted into the left subclavian artery (LSA). CASE SUMMARY: An 84-year-old man with a history of hypertension was admitted to the Neurology Department of our hospital complaining of dizziness and gait disturbance for more than 1 mo. Computed tomography angiography of the head and neck showed severe stenosis at the proximal LSA and the origin of the left vertebral artery. Magnetic resonance diffusion-weighted imaging of the brain revealed subacute infarctions in cerebellum, occipital lobe and medulla oblongata. He suffered a Stanford type B aortic dissection after the proximal LSA angioplasty with a balloon expandable stent. Thoracic endovascular aortic repair was performed immediately with the chimney technique and he was discharged 20 d later. After exploring the pathogenesis with multimodal imaging analysis, an easily neglected focal intramural hematoma (IMH) in the aorta near the junction of the LSA was found to be the main cause of the IAD. The risk of IAD should be sufficiently evaluated according to the characteristics of aortic arch lesions before the proximal LSA angioplasty. CONCLUSION: Focal aortic IMH is a potential risk factor for IAD during a seemingly simple stenting of the proximal LSA.

Endoscopic needle-knife treatment for symptomatic esophageal Zenker's diverticulum: A meta-analysis and systematic review.

OBJECTIVE: The aim of this study was to assess the efficacy and safety following endoscopic management of Zenker's diverticulum (ZD) using a needle-knife technique. METHODS: A systematic search of PubMed, Embase and Cochrane library databases was performed. All original studies reporting efficacy and safety of needle-knife technique for treatment of ZD were included. Pooled event rates across studies were expressed with summative statistics. Main outcomes, such as rates of immediate symptomatic response (ISR), adverse events and recurrence, were extracted, pooled and analyzed. Heterogeneity among studies was assessed using the R statistic. The random effects model was used and results were expressed with forest plots and summative statistics. RESULTS: Thirteen studies included 589 patients were enrolled. Pooled event rates for ISR, overall complication, bleeding and perforation were 88% (95% confidence interval [CI] 79-94%), 13% (95% CI 8-22%), 5% (95% CI 3-10%) and 7% (95% CI 4-12%), respectively. The pooled data demonstrated an overall recurrence rate of 14% (95% CI 9-21%). Diverticulum size of at least 4 cm and less than 4 cm demonstrated pooled adverse event rates of 17% (95% CI 10-27%) and 7% (95% CI 2-18%), respectively. When using diverticuloscope as an accessory, pooled ISR and adverse events rates were 84% (95% CI 58-95%) and 10% (95% CI 3-26%), respectively. CONCLUSION: Flexible endoscopic procedures using needle-knife offers a relatively safe and effective treatment of symptomatic ZD, especially for ZD of <4 cm in diameter.

Identification and validation of argininosuccinate synthase as a candidate urinary biomarker for major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a debilitating psychiatric mood disorder. However, no objective laboratory-based test is yet available to aid in the diagnosis of this disorder. METHODS: In order to identify urinary protein biomarker candidates for MDD, the differential proteomic analysis of urine samples from first-episode drug-naïve MDD subjects and healthy controls (HC) was carried out by using two-dimensional gel electrophoresis separation followed by MALDI-TOF/TOF-MS/MS identification. Then, the differential expression levels of some candidate proteins were further validated by immunoblot analysis. RESULTS: Through mass spectrometry and database searching, a total of 27 differential proteins were identified, primarily including enzymes, plasma proteins, serpins, and adhesion molecules. Five proteins were selected for subsequent validation by Western blotting. One arginine recycling enzyme - argininosuccinate synthase (ASS1) - was further confirmed to be significantly downregulated in the urine of 30 depressed subjects while remaining unchanged in the plasma. Importantly, receiver-operator curve analyses revealed that ASS1 displayed strong efficacy in distinguishing MDD subjects from HC. CONCLUSION: The present study provides a range of urinary protein biomarker candidates for MDD, and further demonstrates that ASS1 has a potential for clinical diagnosis of this disorder.

Combined Metabolomics and Proteomics Analysis of Major Depression in an Animal Model: Perturbed Energy Metabolism in the Chronic Mild Stressed Rat Cerebellum.

Major depressive disorder (MDD) is a highly prevalent, debilitating mental illness of importance for global health. However, its molecular pathophysiology remains poorly understood. Combined proteomics and metabolomics approaches should provide a comprehensive understanding of MDD's etiology. The present study reports novel "-omics" insights from a rodent model of MDD. Cerebellar samples from chronic mild stressed (CMS)-treated depressed rats and controls were compared with a focus on the differentially expressed proteins and metabolites using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics and gas chromotography/mass spectrometry (GC-MS) metabolomics techniques, respectively. The combined analyses found significant alterations associated with cerebellar energy metabolism, as indicated by (1) abnormal amino acid metabolism accompanied by corresponding metabolic enzymatic alterations and disturbed protein turnover, (2) increased glycolytic and tricarboxylic acid (TCA) cycle enzyme levels paralleled by changes in the concentrations of associated metabolites, and (3) perturbation of ATP biosynthesis through adenosine accompanied by perturbation of the mitochondrial respiratory chain. To the best of our knowledge, this study is the first to integrate proteomics and metabolomics analyses to examine the pathophysiological mechanism(s) underlying MDD in a CMS rodent model of depression. These results can offer important insights into the pathogenesis of MDD.

[Ion fluorescence probe detecting the formation of triplex DNA].

The fluorescence of Tb3+ is not quenched after the rare earth ion is combined with DNA. The fluorescence intensity is related not only to the kinds of bases of DNA but also to the kinds of DNA. The rare earth ion Tb3+ was used as the fluorescence probe to detect the formation of triplex DNA. The results show that the fluorescence intensity of Tb3+ combined with polydA is much stronger than that of Tb3+ combined with polydT, which testifies that the fluorescence intensity is related to the kinds of bases combined with Tb3+. The results also demonstrate that the rare earth ion can be used to detect those three forms of DNA though their fluorescence peak positions are similar when Tb3+ as a fluorescence probe is combined with single strand DNA (ssDNA), double helix DNA (dsDNA), and triple helix DNA (tsDNA), respectively. However, their intensities are quite different. The fluorescence intensity of Tb3+ combined with ssDNA-Tb3+ is the largest. And the fluorescence intensity of Tb3+ combined with tsDNA-Tb3+ takes the second place. The minimum peak intensity belongs to the contribution of Tb3+ coupled with dsDNA-Tb3+. The reason is that the capability of energy transference of ssDNA, dsDNA and tsDNA is different. The different degree of energy transference influences the intensities of Tb3+. The influences of pH and the metal ion on the formation of triplex DNA were also studied. The authors found that the neutral pH and high valence metal ion are beneficial to the formation of ts-DNA.

[Residues and health risk assessment of sulfonamides in sediment and fish from typical marine aquaculture regions of Guangdong Province, China].

Concentrations of sulfonamides including sulfadiazine (SDZ), sulfadimidin (SM2) and sulfamethoxazole (SMX) in sediments, muscle and liver tissues of 7 kinds of fish species collected from two marine aquaculture regions along the coast of Guangdong Provice were determined by high performance liquid chromatography (HPLC) equipped with a ultraviolet detector. Assessment of the health risks were conducted based on the values of maximum residue limits (MRL) and acceptable daily intake (ADI). The results showed that sulfonamides were found in all the sediment samples. The concentrations (dry wet) ranged from 2.1 - 35.2 ng x g(-1), the detected frequency of the 3 sulfonamide antibiotics ranked as SDZ (85.7%) > SM2 (71.4%) > SMX (28.6%). The detection rate of sulfonamides in samples from Daya Bay was higher than that from Hailing Island. Higher concentrations were detected in liver tissues rather than in muscle tissues (P < 0.05). The residues of SDZ, SM2 and SMX in fish muscle tissues (wet weight) ranged from 11.6-37.9, 16.3-27.8 and 4.9-20.0 ng x g(-1), respectively. The calculated daily intakes of sulfonamides in the present study ranged from 3.37-36.72 ng x kg(-1), which accounted for 0.007% -0.073% of the ADI (50 microg x kg(-1)). Health risks to human body were negligible as the estimated intake was less than 1% ADI, therefore the security of dietary was high.

Combined application of NMR- and GC-MS-based metabonomics yields a superior urinary biomarker panel for bipolar disorder.

Bipolar disorder (BD) is a debilitating mental disorder that cannot be diagnosed by objective laboratory-based modalities. Our previous studies have independently used nuclear magnetic resonance (NMR)-based and gas chromatography-mass spectrometry (GC-MS)-based metabonomic methods to characterize the urinary metabolic profiles of BD subjects and healthy controls (HC). However, the combined application of NMR spectroscopy and GC-MS may identify a more comprehensive metabolite panel than any single metabonomic platform alone. Therefore, here we applied a dual platform (NMR spectroscopy and GC-MS) that generated a panel of five metabolite biomarkers for BD-four GC-MS-derived metabolites and one NMR-derived metabolite. This composite biomarker panel could effectively discriminate BD subjects from HC, achieving an area under receiver operating characteristic curve (AUC) values of 0.974 in a training set and 0.964 in a test set. Moreover, the diagnostic performance of this panel was significantly superior to the previous single platform-derived metabolite panels. Thus, the urinary biomarker panel identified here shows promise as an effective diagnostic tool for BD. These findings also demonstrate the complementary nature of NMR spectroscopy and GC-MS for metabonomic analysis, suggesting that the combination of NMR spectroscopy and GC-MS can identify a more comprehensive metabolite panel than applying each platform in isolation.

Sex-specific urinary biomarkers for diagnosing bipolar disorder.

Sex-based differences are prominent in affective disorders, but there are no biomarkers available to support sex-specific, laboratory-based diagnostics for male and female bipolar disorder (BD) patients. Here, a NMR-based metabonomic approach was used to preliminarily identify sex-specific urinary metabolite biomarkers for diagnosing male and female BD patients. A male-specific biomarker panel consisting of four metabolites (α-hydroxybutyrate, choline, formate, and N-methylnicotinamide) effectively discriminated between male BD and healthy controls (HC) subjects, achieving an area under the receiver operating characteristic curve (AUC) of 0.942. A female-specific biomarkers panel consisting of four metabolites (α-hydroxybutyrate, oxalacetate, acetone, and N-methylnicotinamide) effectively discriminated between female BD and HC subjects, achieving an AUC of 0.909. The male-specific biomarker panel displayed low discriminatory power in the female group, and the female-specific biomarker panel displayed low discriminatory power in the male group. Moreover, several other metabolites showed different trends between male and female BD subjects. These findings suggest that male and female BD patients have distinct biomarker fingerprints and that these two sex-specific biomarker panels may serve as effective diagnostic tools in distinguishing male and female BD patients from their healthy counterparts. Our work may provide a window into the mechanisms underlying the pathoetiology of BD in both men and women.

[Investigation of quinolones in aquaculture environment of the Pearl River Delta].

The concentrations and distributions of three sorts of quinolones (norfloxacin, ciprofloxacin and enorfloxacin) in water, sediments and the tissues of 8 kinds of fishes from 7 sites in Pearl River Delta aquaculture regions (freshwater and marine) were determined by high performance liquid chromatography (HPLC) with fluorescence detector. Results showed that no quinolones were found in either fresh waterborne or marine water. Norfloxacin, ciprofloxacin and enorfloxacin in sediments collected from freshwater aquaculture region ranged from 5.03-13.28, 3.64-9.32 and 0-7.13 ng x g(-1), respectively, ranged from 1.88-8.81, 0-1.09 ng x g(-1) in marine aquaculture area, respectively. Enorfloxacin were not found in sediments from marine aquaculture. Three kinds of quinolones in liver tissues were higher than that in muscle tissues. The residues of norfloxacin, ciprofloxacin and enorfloxacin in fish muscle tissues ranged from 1.95-100.54, 0.48-33.26 and 1.18-51.89 ng x g(-1), respectively. The concentration of pharmaceuticals in fish tissues were ranked by size as following: norfloxacin, ciprofloxacin and enofloxacin. Higher concentration of quinolones was found in fish from freshwater aquaculture than marine aquaculture.