Fluoroscopy-guided gastric peroral endoscopic pyloromyotomy (G-POEM): a more reliable and efficient method for treatment of refractory gastroparesis.

INTRODUCTION: Prior studies show promising results of the gastric peroral endoscopic pyloromyotomy (G-POEM) procedure for treatment of refractory gastroparesis. One major technical challenge involved in this procedure is identifying the pyloric muscular ring (PMR). The aim of this study is to establish a reliable method for identification of the PMR during G-POEM. METHODS: Fluoroscopy-guided G-POEM was performed by placing an endoclip at the 9 to 11'o clock position at the pylorus for identification of PMR. Conventional G-POEM was performed by observation of blue colored mucosa at the pylorus area as an indirect marker for PMR. The degree of the PMR identification was graded into well identified, identified, and not identified based on the appearance of the PMR. Procedure times were accurately documented. Gastroparesis cardinal symptoms index and gastric emptying scintigraphy were evaluated before and after the procedure. RESULTS: Fourteen patients were studied, seven underwent fluoroscopy-guided G-POEM, and seven patients underwent conventional G-POEM. All procedures achieved technical success and no adverse events occurred. In the seven patients who underwent fluoroscopy-guided G-POEM, the PMR was well identified in four patients and identified in three patients. In the seven patients who underwent conventional G-POEM, the PMR was identified in four patients and not identified in three patients. The average time to complete the fluoroscopy-guided G-POEM was significantly shorter than that of the conventional G-POEM. CONCLUSIONS: Fluoroscopy-guided G-POEM by placement of an endoclip at the pylorus was a reliable and safe method to direct the orientation of the submucosal tunnel, to facilitate the location of the PMR, and to shorten the procedure time.

Common polymorphisms of the microRNA genes (miR-146a and miR-196a-2) and gastric cancer risk: an updated meta-analysis.

The associations between two common polymorphisms in microRNA genes (miR-146a, dbSNP: rs2910164; miR-196a-2, dbSNP: rs11614913) and gastric cancer risk have frequently been examined; however, the results have often been controversial. This meta-analysis was performed to clarify the association between the two polymorphisms and gastric cancer risk. The literature search primarily utilized PubMed, Embase, SinoMed, and Wanfang databases to identify eligible studies. Odds ratios (ORs) with their 95% confidence intervals (CIs) were analyzed to investigate possible correlations. Subgroup analyses of ethnicity as well as source of controls were also performed. The correlation analysis was based on 11 studies, containing 4690 patients and 6066 controls for miR-146a (C>G) together with 1911 patients and 2484 controls for miR-196a-2 (T>C). For the miR-146a polymorphism, the values of the ORs and 95%CIs were >1, suggesting that a correlation exists. In subgroup analysis of source of controls, a correlation was also identified in the Asian subgroup. However, in Caucasians the ORs and 95%CIs were not distributed on the same side of the critical value 1, contra-indicative of a correlation in this group. For the miR-196a-2 polymorphism, the ORs with 95%CIs of both overall and subgroup analyses were also not restricted to >1 or ˂1. In summary, the results suggested that the miR-146a rs2910164 polymorphism was related to gastric cancer risk in Asians but not in Caucasians, and no distinct correlation seemed to exist between the miR-196a-2 rs11614913 polymorphism and the risk of gastric cancer.

Regulatory T cells in the pathogenesis of type 2 diabetes mellitus retinopathy by miR-155.

OBJECTIVE: To explore the regulatory T cells (Treg) in the peripheral blood of diabetic retinopathy patients by microRNA-155 (miR-155), and investigate the mechanisms of regulatory T cells and miR-155 in the pathogenesis of diabetic retinopathy. PATIENTS AND METHODS: The study explores the percentage of CD4+ CD25+ Foxp3+ T cells (Treg cells) and the expression of miR-155 in the peripheral blood of 20 cases with background diabetic retinopathy (BDR group) and 20 cases with proliferative diabetic retinopathy (PDR group). Flow cytometry and RT-PCR determined 18 cases with non-diabetic retinopathy (NDR group) and 20 cases of healthy control (NC group). ELISA determined the expression of TGF-ß. RESULTS: The percentages of Treg cells in the peripheral blood of patients in BDR group, PDR group, and NDR group had significantly decreased compared to that in the NC group (p < 0.05). The percentages of the Treg cells in the BDR and PDR groups were lower than those in NDR group (p < 0.05 in both cases). The percentage of Treg cells in the PDR group was lower than that in the BDR group (p < 0.05). The expression levels of miR-155 in the peripheral blood of the patients in the BDR group, PDR group, and NDR group had significantly increased compared to that in NC group (p < 0.05). The expression levels of miR-155 in the BDR group and PDR group were higher than that in the NDR group (p < 0.05 in both cases). The expression level of miR-155 in the PDR group was higher than that in the BDR group (p < 0.05). The expression levels of TGF-ß in the BDR group and PDR group were significantly decreased compared to those in the NDR group and NC group (p < 0.05 in both cases). The expression of miR-155 was negatively related to the Treg cells and the expression level of TGF-ß2 (r1 = -0.835, p1 = 0.000, r2 = -0.771, p2 = 0.000). CONCLUSIONS: In type 2 diabetes mellitus (T2DM) retinopathy, miR-155 may play an important role in the pathogenesis of T2DM retinopathy by regulating the Treg cells with TGF-ß.

MicroRNA-155 may be involved in the pathogenesis of atopic dermatitis by modulating the differentiation and function of T helper type 17 (Th17) cells.

Our aims were to identify the differential expression of microRNA (miR)-155, as well as to explore the possible regulatory effects of miR-155 on the differentiation and function of T helper type 17 (Th17) cells in atopic dermatitis (AD). The Th17 cell percentage and expression levels of miR-155, retinoic acid-related orphan receptor (ROR)γt, interleukin (IL)-17 and suppressor of cytokine signalling-1 (SOCS1) in peripheral CD4(+) T cells, plasma and skin specimens were detected and compared in AD patients and healthy subjects. A miR-155 mimic and an inhibitor were transfected separately into AD CD4(+) T cells to confirm the in-vivo data. The Th17 cell percentage, miR-155 expression, RORγt mRNA expression, IL-17 mRNA expression and plasma concentration were increased significantly in AD patients compared with healthy subjects. Conversely, SOCS1 mRNA expression and plasma concentration were decreased significantly. Similar results were detected in cultured CD4(+) T cells transfected with the miR-155 mimic compared with a miR-155 inhibitor or a negative control. Additionally, there was a sequential decrease in miR-155 expression, as well as RORγt and IL-17 mRNA expression, but an increase in SOCS1 mRNA expression, from AD lesional skin and perilesional skin to normal skin. Positive correlations were found between miR-155 expression and AD severity, Th17 cell percentage, RORγt mRNA expression and IL-17 mRNA expression and plasma concentration, while negative correlations were observed between miR-155 expression and SOCS1 mRNA expression and plasma concentration in AD peripheral circulation and skin lesions. In conclusion, miR-155 is over-expressed and may be involved in AD pathogenesis by modulating the differentiation and function of Th17 cells.

Loop-locked coherent population trapping magnetometer based on a fiber electro-optic modulator.

We have set up a coherent population trapping (CPT)-based magnetometer prototype with the D1 line of 87Rb atoms. The dichromatic light field is derived from a fiber electro-optic modulator (FEOM) connected to an external cavity laser diode. A CPT resonance signal with a 516 Hz linewidth is observed. By feeding back the derivative of the resonance curve to the FEOM with a proportional integral controller, of which the voltage output is directly converted to the measured magnetic field intensity, the resonance peak is locked to the environmental magnetic field. The measurement data we have achieved are well matched with the data measured by a commercial fluxgate magnetometer within 2 nT, and the sensitivity is better than 8 pT/√Hz in a parallel B field.

Possible pathogenic role of T helper type 9 cells and interleukin (IL)-9 in atopic dermatitis.

T helper type 9 (Th9) cells are a novel identified subset of CD4(+) T helper cells, which could partly contribute to allergic inflammation, while the precise contribution of Th9 cells in atopic dermatitis (AD) remains unknown. We aimed to explore the possible role of Th9 cells in AD pathogenesis. The Th9 cell percentage, transcription factor PU.1 and cytokine interleukin (IL)-9 mRNA levels, as well as IL-9 serum concentration in peripheral circulation, were measured in AD patients, psoriasis patients and healthy controls. The Th9 cell percentage, PU.1 and IL-9 expression levels of AD patients were all increased significantly compared with the other two control groups (P < 0·01), and correlated positively with SCORing Atopic Dermatitis index, serum immunoglobulin (Ig)E and thymus- and activation-regulated chemokine (TARC) levels (P < 0·05). In simple AD patients and AD patients complicated by allergic rhinitis or asthma, there were no significant differences in the Th9 cell percentage, PU.1 and IL-9 expression levels between them. At the same time, IL-9 and vascular endothelial growth factor (VEGF) mRNA levels were detected in AD lesions and normal skin samples, which were both distinctly elevated in AD lesions, and there was a positive association between them (P < 0·01). Keratinocytes were cultured with IL-9 stimulation and the secretion of VEGF was detected. IL-9 can promote the secretion of VEGF by keratinocytes in a time- and dose-dependent manner. In conclusion, the expansion of the Th9 cell subset, up-regulation of the PU.1 transcription factor and increased secretion of the IL-9 cytokine may contribute to the pathogenesis of AD, which may be supported by the increased release of VEGF by keratinocyes after IL-9 stimulation.

The Imbalance of Th17 cells and CD4(+) CD25(high) Foxp3(+) Treg cells in patients with atopic dermatitis.

BACKGROUND: Th17/Treg imbalance is involved in several autoimmune, inflammatory and allergic reactions. Nevertheless, the possible contribution of Th17/Treg imbalance in atopic dermatitis (AD) remains unknown. OBJECTIVE: To explore the possible role of Th17/Treg imbalance in AD. METHODS: Th17 and Treg cells percentage in peripheral blood mononuclear cells (PBMCs) and skin specimens, specific transcription factor retinoic acid-related orphan receptor (ROR)γt and Foxp3 mRNA levels in PBMCs, as well as Th17- and Treg-related cytokines mRNA levels in PBMCs, serum concentrations, and expression levels in PBMCs culture supernatant after recombinant Dermatophagoides pteronyssinus antigen stimulation were detected in AD patients. Controls included patients with psoriasis, allergic contact dermatitis (ACD) and healthy donors. RESULTS: Th17 cells percentage, RORγt, IL-17 and IL-23 levels in peripheral circulation of AD patients were significantly higher than those in ACD patients and healthy controls, but lower than those of psoriasis patients. Treg cells percentage, Foxp3 and TGF-ß mRNA levels were reduced in AD patients compared with healthy controls, while there were no significant differences among AD, ACD and psoriasis patients. Th17 cells percentage, IL-17 and IL-23 levels were increased, while Treg cells percentage and TGF-ß level were decreased in AD lesion and PBMCs culture supernatant respectively. There was a negative association between Th17 and Treg cells percentage in AD patients. AD severity score positively correlated with Th17 cells percentage and Th17/Treg ratio, while negatively correlated with Treg cells percentage. Serum IgE levels positively correlated with Th17/Treg ratio. CONCLUSION: In AD, there exists an immune imbalance in Th17 and Treg cells, which may contribute to its pathogenesis and development.

Note: Generation of Raman laser beams based on a sideband injection-locking technique using a fiber electro-optical modulator.

Two phase-coherent Raman laser beams with a frequency offset of 6.835 GHz were generated by sideband injection-locking technique. A master diode laser was phase-modulated at 6.835 GHz by a fiber electro-optic modulator. A slave diode was injection-locked to the -1 sideband of the phase-modulated beam, and another diode was locked to the master laser carrier. This method produced stable and spatially separated Raman lasers with a large frequency shift range (>180 MHz). The relative linewidth of these two beams was ∼1 Hz, and the unwanted carrier mode was suppressed down to -24 dB. Stimulated Raman transitions and Ramsey fringes were driven by Raman lasers in a cold atomic beam.

Application of magnifying endoscopy with narrow-band imaging in diagnosing gastric lesions: a prospective study.

BACKGROUND: Magnifying endoscopy with narrow-band imaging (ME-NBI) can more clearly assess the surface pattern and microvascular architecture of gastric lesions. OBJECTIVE: To evaluate the diagnostic efficacy of ME-NBI in patients with early gastric cancer. DESIGN: Prospective study. SETTING: Single academic center. PATIENTS: This study involved 164 suspected gastric lesions in 146 consecutive patients who underwent ME-NBI for additional differential diagnosis before treatment. INTERVENTION: ME-NBI findings were classified into 3 groups based on irregularities, absence of surface pattern, and microvascular architecture. All lesions were treated endoscopically or surgically, and ME-NBI diagnosis was compared with histopathological findings. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of real-time ME-NBI diagnosis were determined. RESULTS: The sensitivity, specificity, and accuracy of ME-NBI were 97.3%, 84.4%, and 90.2%, respectively, in distinguishing between cancerous and noncancerous lesions and were 92.3%, 89.7%, and 90.4%, respectively, in distinguishing undifferentiated from differentiated adenocarcinoma. ME-NBI accurately predicted depth of invasion in 37 of 39 differentiated adenocarcinomas (95%). LIMITATIONS: The sample size was relatively small. CONCLUSIONS: ME-NBI can successfully distinguish between cancerous and noncancerous lesions and between undifferentiated and differentiated adenocarcinomas. Of the 3 patterns on ME-NBI, type A is mainly characteristic of noncancerous lesions, type B is a good indicator of differentiated adenocarcinoma and intramucosal/superficially invasive cancers, and type C is indicative of undifferentiated adenocarcinoma or differentiated cancer with deep submucosal invasion.

A pilot study of endoscopic spray cryotherapy by pressurized carbon dioxide gas for Barrett's esophagus.

BACKGROUND AND STUDY AIMS: Endoscopic spray cryoablation is a novel approach for the treatment of Barrett's esophagus. However, few studies have reported its efficacy, especially with the use of carbon dioxide (CO (2)). The aim of the current study was to evaluate the short term efficacy and complications using CO (2) in endoscopic cryoablation of Barrett's esophagus. METHODS: Patients diagnosed with Barrett's esophagus underwent monthly stepwise cryoablation with pressurized CO (2) gas, with follow-up esophageal biopsies until complete histological reversal was achieved. Responses were analyzed with an intention-to-treat analysis according to complete response for intestinal metaplasia (CR-IM), which was defined as the elimination of all intestinal metaplasia including specialized intestinal metaplasia (SIM), subsquamous SIM, and dysplasia with intestinal metaplasia in the biopsies under narrow-band imaging (NBI). RESULTS: In total, 22 patients were enrolled, 20 of whom completed the treatment. Two patients declined further ablation after the first cryotherapy session. A total of 44 sessions were performed; a median of 2 sessions per patient (range 1 - 3 sessions) were needed to complete the ablation of Barrett's esophagus. No severe complications occurred. Follow-up endoscopies were performed in 20 patients (90.9 %). Two patients (9.1 %) were lost to follow-up. Median follow-up was 10 months (range 6 - 18 months). After cryotherapy, 20 patients (90.9 %) reached CR-IM of Barrett's esophagus. Patients underwent a median number of 3 follow-up endoscopies (range 2 - 4) with biopsies. At 6 months, recurrence was evident in three patients (13.6 % of the overall population, 15.0 % of the CR-IM population). One of the three patients developed intestinal metaplasia but no dysplastic change and the other two developed subsquamous SIM. CONCLUSIONS: The pressurized CO (2) spray cryotherapy is a relatively effective and safe endoscopic treatment for Barrett's esophagus.

Potent antitumoral efficacy of a novel replicative adenovirus CNHK300 targeting telomerase-positive cancer cells.

PURPOSE: Telomerase reverse transcriptase (hTERT) is the key determinant of telomerase activity and plays a crucial role in cellular immortalization and oncogenesis. It will be a promising target for cancer gene therapy. We constructed a novel replicative adenovirus CNHK300 in which hTERT promoter with three extra E-boxes downstream of the promoter was introduced and used to regulate adenoviral E1a gene, and studied its properties of selective replication in cancer cells and antitumoral activity. METHODS: Luciferase assay was used to detect hTERT promoter activity. The selective replication of CNHK300 in cancer cells was investigated by E1a Western blot and green fluorescent protein (GFP) reporter gene assay. The antitumoral activity of CNHK300 and its toxicity were measured on animal models. RESULTS: Luciferase assay showed that introducing extra E-boxes downstream of hTERT promoter is beneficial to decreasing the promoter activity in normal cells without affecting its strong activity in cancer cells. Experiments in vitro and in vivo demonstrated that CNHK300 can selectively target to hTERT-positive cancer cells and replicate in them, resulting in oncolytic or antitumoral effect. CNHK300 is superior to ONYX-015 in terms of selective replication and oncolytic or antitumoral effect. The toxicity assay showed no signs of toxicity to liver cells even at the higher dosage of CNHK300 in vivo. CONCLUSION: The hTERT promoter-controlled, replication-competent adenovirus CNHK300 is a promising system for targeted cancer gene therapy.

Nickel speciation and complexation kinetics in freshwater by ligand exchange and DPCSV.

A technique of ligand exchange with DMG (dimethylglyoxime) and DPCSV was applied to determine Ni speciation in lake, river, and groundwater samples. The working conditions related to ligand-exchange equilibrium were optimized, and the ligand-exchange kinetics were examined. The observed pseudo-first-order rate, kobsd, was about 3 x 10(-5) (s-1) for Ni(DMG)2 complex formation with an excess of DMG (microM) over Ni (nM) at pH 7.1-7.7. The second-order exchange kinetic constants, kexch, were between 1.2 x 10(2) and 5.7 x 10(3) s-1 M-1 for ligand exchange of NiEDTA with DMG and between 5 x 10(2) and 7 x 10(3) s-1 M-1 for exchange of natural ligands with DMG in the freshwater samples under similar conditions. Ni ligand exchange between natural ligands and DMG occurred over days with half-lifes of 5-95 h. Total dissolved Ni concentrations in samples from various freshwater systems in Switzerland ranged from 4 nM in an oligotrophic lake to 30 nM in a small river affected by inputs from sewage effluents and agriculture. Free ionic Ni2+ concentrations were determined in the range of 10(-13)-10(-15) M (pNi = 12.2-14.7), indicating that more than 99.9% of dissolved Ni was bound by organic ligands with strong affinity (log K 12.1-14.9) and low concentrations (13-100 nM) at pH 7.2-8.2. Because of slow ligand-exchange kinetics, Ni speciation in natural waters may in many cases not reach equilibrium.