Surface maturation scoring for oesophageal squamous intraepithelial neoplasia: a novel diagnostic approach inspired by first endomicroscopic 3-dimensional reconstruction.

OBJECTIVE: Loss of surface maturation and cytonuclear atypia have been regarded as the pathological 'gold standard' for the diagnosis of oesophageal squamous cell intraepithelial neoplasia. However, there has been no satisfactory endomicroscopic method similar to this pathological approach to detect surface maturation and screen for oesophageal squamous cell intraepithelial neoplasia. The aim of this study was to apply a 3-dimensional (3D) confocal endomicroscopic imaging technique to investigate the surface maturation of the oesophageal epithelium and develop new 2-dimensional confocal endomicroscopic criteria based on surface maturation. DESIGN: In the 3D reconstruction phase, intrapapillary capillary loops were reconstructed to demonstrate the stereo configuration of the oesophageal epithelium, and a novel surface maturation scoring (SMS) method for plane confocal images was developed based on the interpretation of the 3D microstructure. In the SMS diagnostic phase, 1214 patients were screened and confocal images from 64 non-invasive oesophageal lesions were independently evaluated using SMS and previous methods. RESULTS: We successfully obtained and interpreted 3D confocal images of the human oesophageal epithelium for the first time. The sensitivity (81.0%, 95% CI 58.1% to 94.6%) and specificity (90.7%, 95% CI 77.9% to 97.4%) of the newly established SMS were superior to previous confocal approaches in distinguishing squamous intraepithelial neoplasia from other non-invasive lesions. CONCLUSIONS: 3D confocal endomicroscopic imaging provides valuable insight into the stereo configuration of the human oesophageal epithelium. SMS is a novel and promising diagnostic method to distinguish neoplasia during ongoing endoscopy.

Brain-derived neurotrophic factor contributes to abdominal pain in irritable bowel syndrome.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, may play a critical role in many chronic pain conditions. The possible involvement of BDNF in the altered gut sensation in patients with irritable bowel syndrome (IBS) was investigated in the present study. METHODS: Rectosigmoid biopsies were collected from 40 patients with IBS fulfilling the Rome II criteria and 21 healthy controls. Abdominal pain was quantified by a validated questionnaire. The presence of BDNF and nerve fibres in the mucosa was assessed by immunohistochemistry. The structure of mucosal nerve fibres was assessed by transmission electron microscopy. Mucosal BDNF release was measured by ELISA and correlated with abdominal pain scores. Animal studies using BDNF(+/-) mice were carried out to evaluate visceral sensitivity, mucosal nerve fibre density and ultrastructural changes. Alterations of visceral sensitivity and TrkB expression in dorsal root ganglia were examined in BDNF(+/+) mice following different doses of BDNF administration. RESULTS: Biopsies from patients with IBS revealed a significant upregulation of BDNF (p=0.003), as compared with controls. Total nerve fibres were also substantially increased in patients with IBS. Electron microscopy showed ultrastructural damage on the mucosal nerve fibres (eg, swollen mitochondria and nerve axons). Elevated BDNF release was significantly correlated with the abdominal pain scores. Meanwhile, abdominal withdrawal reflex scores to colorectal distension and mucosal protein gene product 9.5 immunoreactivity were significantly lowered in BDNF(+/-) than in BDNF(+/+) mice. Electron microscopy showed degenerative changes on the mucosal nerve fibres in BDNF(+/-) mice. Exogenous BDNF induced an obvious dose-dependent increase in TrkB expression in dorsal root ganglia and dose-dependent decrease in threshold pressure in BDNF(+/+) mice. CONCLUSIONS: The increased expression of BDNF in colonic mucosa, together with the structural alterations of mucosal innervation, may contribute to the visceral hyperalgesia in IBS.

Determination of CYP450 activities in diabetes mellitus rats by a UHPLC-MS/MS method.

In this study, we investigated the effect of type 1 diabetes mellitus on the modulation of the activities of CYP450s in dynamics by a UHPLC-MS/MS method. The diabetic rat model was constructed by an intraperitoneal single injection of streptozotocin. Fasting blood glucose levels > 16.7 mmol/L were considered as diabetic. The rats were given a cocktail of four probe drugs (10 mg/kg phenacetin, 1 mg/kg tolbutamide, 10 mg/kg metoprolol, and 10 mg/kg midazolam) by oral administration for the pharmacokinetic study. Thereafter, the metabolic ratio (MR) of the metabolites to probe substrates were determined. The results indicated that two weeks after diabetes was induced, diabetes increased the MRs of acetaminophen/phenacetin (CYP1A2) and 4-hydroxyl tolbutamide/tolbutamide (CYP2C9); however, it decreased the MRs of α-hydroxy metoprolol/metoprolol (CYP2D6) and 1-hydroxy midazolam/midazolam (CYP3A4). Two months after diabetes was induced, diabetes increased the MRs of acetaminophen/phenacetin and 4-hydroxyl tolbutamide/tolbutamide. The MR of α-hydroxy metoprolol/metoprolol was decreased and the MR of 1-hydroxy midazolam/midazolam was increased but the difference was not significant. According to the results, CYP1A2 and CYP2C9 activities were enhanced in the diabetic rats. and CYP2D6 activity was inhibited in a short period of diabetes; however, the decrease in CYP2D6 activity was not significant in the long period. CYP3A4 activity was decreased in a short period of diabetes and increased in a long period of diabetes but was not significant in the two periods. This study suggests the activity change rule of the CYP450 enzyme system in diabetes mellitus, which can provide a reference for precise clinical medication.

Implementation of a motivational programme based on existence- relatedness-growth theory in nursing undergraduate interns: A quasi-experimental study.

BACKGROUND: Currently, a paramount issue in nursing education is to motivate nursing undergraduate interns to develop self-directed learning skills and improve their practice satisfaction and professional identity, so as to meet the growing demands in healthcare. OBJECTIVES: This study aimed to examine the effectiveness of a motivational programme based on the Existence-Relatedness-Growth (ERG) theory in developing self-directed learning skills, improving practice satisfaction and promoting the professional identity of nursing undergraduate interns in China. DESIGN: A quasi-experimental study design. SETTING: A government-funded tertiary teaching hospital in Guangzhou, Guangdong province, China. METHODS: This study was conducted with 99 nursing undergraduate interns in a hospital between June 2020 and April 2022. The interns in the experimental group (n = 50) participated in the motivational programme based on ERG theory, while those in the control group (n = 49) underwent a traditional training programme. The interns in the two groups were compared in terms of their degree of self-directed learning, practice satisfaction and professional identity after the training, using independent samples t-test. RESULTS: After the internship, interns in the experimental group showed a statistically significantly higher level of self-directed learning and practice satisfaction than those in the control group (p < 0.05). However, no significant difference was observed in professional identity between the two groups after the internship. CONCLUSIONS: The motivational programme based on ERG theory was shown to be effective in improving self-directed learning and practice satisfaction in nursing undergraduate interns. A large-scale randomized controlled trial is warranted to confirm the results.

Milk fat globule-epidermal growth factor 8 is decreased in intestinal epithelium of ulcerative colitis patients and thereby causes increased apoptosis and impaired wound healing.

Milk fat globule-epidermal growth factor 8 (MFG-E8) plays an important role in maintaining intestinal barrier homeostasis and accelerating intestinal restitution. However, studies of MFG-E8 expression in humans with ulcerative colitis are lacking. We examined MFG-E8 expression in colonic mucosal biopsies from ulcerative colitis patients and healthy controls (n = 26 each) by real-time quantitative polymerase chain reaction (PCR), Western blot analysis and immunohistochemistry. MFG-E8 mRNA and protein expression was lower in ulcerative colitis patients than in controls. MFG-E8 expression was inversely correlated with mucosal inflammatory activity and clinical disease activity in patients. MFG-E8 was present in human intestinal epithelial cells both in vivo and in vitro. Apoptosis induction was also detected in the intestinal epithelium of ulcerative colitis patients by terminal-deoxynucleoitidyl transferase mediated nick-end labeling assay. We used lentiviral vectors encoding human MFG-E8 targeting short hairpin RNA to obtain MFG-E8 knockdown intestinal epithelia cell clones. MFG-E8 knockdown could promote apoptosis in intestinal epithelial cell lines, accompanied by a decrease in level of the antiapoptotic protein B-cell lymphoma 2 (BCL-2) and induction of the proapoptotic protein BCL2-associated protein X (BAX). The addition of recombinant human MFG-E8 led to decreased BAX and cleaved caspase-3 levels and induction of BCL-2 level in intestinal epithelia cells. MFG-E8 knockdown also attenuated wound healing on scratch assay of intestinal epithelial cells. The mRNA level of intestinal trefoid factor 3, a pivotal factor in intestinal epithelial cell migration and restitution, was downregulated with MFG-E8 knockdown. In conclusion, we demonstrated that decreased colonic MFG-E8 expression in patients with ulcerative colitis may be associated with mucosal inflammatory activity and clinical disease activity through basal cell apoptosis and preventing tissue healing in the pathogenesis of ulcerative colitis.

Synthesis and characterization of Ag@AgCl-reinforced cellulose composites with enhanced antibacterial and photocatalytic degradation properties.

In the present work, Ag@AgCl-reinforced cellulose composites with enhanced antibacterial and photocatalytic degradation properties were successfully synthesized via oil bath heating method. During the process, zinc chloride (ZnCl2) solution was used as both Cl- resource to form AgCl and the solvent to dissolve cellulose. The samples were synthesized with different temperatures, times, and concentrations of ZnCl2 solution. The morphology, microstructure and phase of the as-prepared samples were analyzed with X-ray powder diffraction (XRD), fourier transform infrared (FTIR) spectrometry, scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HR-TEM), X-ray photoelectron spectroscopy (XPS), photocatalytic activity studies and inhibition zone experiments. Results showed that dye solution could be completely degraded by the materials in 1 h, and higher concentrations of ZnCl2 solution favored for larger inhibition zones (higher to 10.8 mm). This synthetic strategy displayed here offers more possibilities to high value-added applications of cellulose.

Microwave-assisted alkali hydrolysis for cellulose isolation from wheat straw: Influence of reaction conditions and non-thermal effects of microwave.

Microwave-assisted hydrolysis has been widely studied for cellulose fiber isolation, but the influence of reaction conditions and the microwave non-thermal effect are not well clarified. In this study, a series of well-designed experiments were carried out to measure the effects of reaction conditions including temperature, duration and alkali concentration. Compared to the other parameters, temperature was more relevant to the cellulose content in fiber. It could reach the maximum purity of 90.66 % when the temperature was up to 140 °C. Moreover, the existence of non-thermal effect of microwave has been confirmed through extensive determination and characterization of the fibers obtained from parallel controlled experiments conducted with or without microwave assistance. Approximately 50 %-75 % reduction in reaction time or 67 % of that in chemical costs would be realized under microwave with respect to traditional heating hydrolysis. Therefore, this work provides both deep insight and efficiency strategy into the microwave-assisted cellulose isolation.

Determination of Anlotinib, a Tyrosine Kinase Inhibitor, in Rat Plasma by UHPLC-MS/MS and Its Application to a Pharmacokinetic Study.

Anlotinib is a novel inhibitor of receptor kinase tyrosine with multitargets and has a broad spectrum of inhibitory action on tumor angiogenesis and growth. A simple and rapid UHPLC-MS/MS bioanalytical method was validated for the determination of anlotinib in rat plasma, using imatinib as an internal standard. An Acquity BEH C18 column was used to separate analytes. The eluents consisted of formic acid/water (0.1 : 100, v/v) and acetonitrile with a mobile phase. A triple quadrupole mass spectrometer was operated for the quantification with multiple reaction monitoring (MRM) to determine transitions: 408.2 ⟶ 339.1 for anlotinib, and 494.3 ⟶ 394.1 for imatinib. The validated range was 0.1-50 ng/mL for anlotinib. Mean recovery rate of anlotinib in plasma was ≥99.32% and reproducible. Also, the intra- and interday precisions were both below 15%. This robust method was successfully applied to support the pharmacokinetic study of anlotinib in rats.

A fluorescent chemosensor for copper(II) based on a carboxylic acid-functionalized tris(2,2'-bipyridine)-ruthenium(II) complex.

In this research, bis(2,2'-bipyridine)(4-methyl-2,2'-bipyridine-4'-carboxylic acid)ruthenium(II).2PF(6)- complex (1), was first used as a fluorescent chemosensor to recognize Cu(II) in EtOH/H(2)O (1:1, v/v) solution. The response of the sensor is based on the fluorescence quenching of complex 1 by binding with Cu(II). The analytical performance characteristics of the proposed Cu(II)-sensitive chemosensor were investigated. The sensor can be applied to the quantification of Cu(II) with a linear range covering from 5.0 x 10(-8) to 1.0 x 10(-4) M and a detection limit of 4.2 x 10(-8) M. The experiment results show that the response behavior of 1 to Cu(II) is pH independent in medium condition (pH 4.0 - 8.0), and show excellent selectivity for Cu(II) over other transition metal cations.

Understanding the mechanism of ultrasound on the synthesis of cellulose/Cu(OH)2/CuO hybrids.

Understanding the mechanism of ultrasound from metal hydroxide to oxides via an ultrasound irradiation method is of great importance for broadening and improving their synthesis and industrial applications. The purpose of this article was to explore the mechanism of ultrasound on the synthesis of cellulose/Cu(OH)2/CuO hybrids. The influences of various reaction parameters including the volume of H2O2, heating method, pulse mode of ultrasound irradiation, sonication time, and power density on the cellulose/Cu(OH)2/CuO hybrids were investigated in detail by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectra (EDS), thermogravimetric analysis (TGA), and derivative thermogravimetry (DTG). The experimental results indicated that all the parameters have effects on the cellulose/Cu(OH)2/CuO hybrids, power density had an effect on the phase transformation of Cu(OH)2 to CuO, and the addition of H2O2 played an important role in the shape of cellulose hybrids, which provided an indirect evidence on the H2O2-induced oxidation route for the transformation process from Cu(OH)2 to CuO during the ultrasound irradiation process. These results maybe direct the synthesis and potential applications of cellulose hybrids in the near future.

Compare study cellulose/Ag hybrids using fructose and glucose as reducing reagents by hydrothermal method.

The primary objective of this work was to evaluate the effect of reducing reagents on the hybrids from cellulose and Ag, which have been successfully synthesized by using fructose and glucose as reducing reagents via a hydrothermal method, respectively. The hybrids were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential thermal analysis (DTA). The influences of the various reaction parameters including the heating time, heating temperature, and types of reducing reagents on the hybrids were investigated. Silver particles can be better dispersed in the cellulose matrix by adjusting reaction parameters. Experimental results demonstrated that the types of reducing reagents played an important role in the shape and dispersion of silver particles in hybrids.

Environmentally-friendly sonochemistry synthesis of hybrids from lignocelluloses and silver.

The purpose of this study was to explore a green strategy about the high value-added applications of biomass. Hybrids from lignocelluloses and silver have been successfully prepared using NaBH4 as reducing reagent by an environmentally-friendly sonochemistry method. The phase, microstructure, and morphology of the hybrids were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential thermal analysis (DTA). The influences of the various reaction parameters including reaction time, lignocelluloses concentration, and types of reducing reagents on the products were investigated in detail. Silver particles can be better dispersed on the lignocelluloses matrix by adjusting reaction parameters. These hybrids may be a promising antimicrobial material for their applications in the biomedical field. This environmentally-friendly synthetic strategy reported here opens a new window to the high value-added applications of lignocelluloses.

Environmentally friendly ultrosound synthesis and antibacterial activity of cellulose/Ag/AgCl hybrids.

This study aims to investigate the fabrication and property of cellulose/Ag/AgCl hybrids. In this article, preparation of cellulose/Ag/AgCl hybrids was reported using the cellulose solution, AgNO3, AlCl3·6H2O with ultrasound agitation method. The cellulose solution was synthesized by the dissolution of the microcrystalline cellulose in NaOH/urea aqueous solution. Influences of the experimental parameters of ultrasound treatment time and ultrasonic intermittent on the hybrids were investigated. The phase, microstructure, thermal stability, and morphology of the hybrids were characterized by X-ray powder diffraction (XRD), Fourier transform infrared (FTIR) spectrometry, thermogravimetric analysis (TGA), differential thermal analysis (DTA), and scanning electron microscopy (SEM). Results showed the successful synthesis of cellulose/Ag/AgCl hybrids with good thermal stability. Moreover, the hybrids displayed desirable antimicrobial activities. Compared with other conventional methods, the rapid, green, and environmentally friendly ultrasound agitation method opens a new window to the high value-added applications of biomass.

Learning curve and interobserver agreement of confocal laser endomicroscopy for detecting precancerous or early-stage esophageal squamous cancer.

BACKGROUND: Confocal laser endomicroscopy (CLE) can provide in vivo subcellular resolution images of esophageal lesions. However, the learning curve in interpreting CLE images of precancerous or early-stage esophageal squamous cancer is unknown. The goal of this study is to evaluate the diagnostic accuracy and inter-observer agreement for differentiating esophageal lesions in CLE images among experienced and inexperienced observers and to assess the learning curve. METHOD: After a short training, 8 experienced and 14 inexperienced endoscopists evaluated in sequence 4 sets of high-quality CLE images. Their diagnoses were corrected and discussed after each set. For each image, the diagnostic results, confidence in diagnosis, quality and time to evaluate were recorded. RESULTS: Overall, diagnostic accuracy was greater for the second, third, fourth set of images as compared with the initial set (odds ratio [OR] 2.01, 95% CI 1.22-3.31; 7.95, 3.74-16.87; and 6.45, 3.14-13.27), respectively, with no difference between the third and fourth sets in accuracy (p = 0.67). Previous experience affected the diagnostic accuracy only in the first set of images (OR 3.70, 1.87-7.29, p<0.001). Inter-observer agreement was higher for experienced than inexperienced endoscopists (0.732 vs. 0.666, p<0.01). CONCLUSION: CLE is a promising technology that can be quickly learned after a short training period; previous experience is associated with diagnostic accuracy only at the initial stage of learning.

Compare study CaCO3 crystals on the cellulose substrate by microwave-assisted method and ultrasound agitation method.

The purposes of this article were to investigate the influences of synthesis strategy on the CaCO(3) crystals on the cellulose substrate. In this study, CaCO(3) crystals were synthesized using cellulose as matrix by the microwave-assisted method and ultrasound agitation method, respectively. The CaCO(3) crystals on the cellulose substrate were characterized by means of X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Experimental results demonstrated that the synthesis strategy had a dramatically influences on the phase, microstructure, morphology, thermal stability, and biological activity of the CaCO(3) crystals. The pure phase of vaterite spheres with the diameter of about 320-600nm were obtained by ultrasound agitation method, meanwhile, the mixed phases of calcite and vaterite with the diameter of about 0.82-1.24µm were observed by microwave-assisted method. In view of experimental results, one can conclude that the ultrasound agitation method do more favors to the synthesis of CaCO(3) crystals with uniform morphology and size, compared with microwave-assisted method. Furthermore, cytotoxicity experiments indicated that the CaCO(3) crystals on the cellulose substrate had good biocompatibility and could be a candidate for the biomedical applications.

Cellulose/CaCO3 nanocomposites: microwave ionic liquid synthesis, characterization, and biological activity.

The purposes of this article are to synthesize the biomass-based hybrid nanocomposites using green method in green solvent and evaluate its biological activity. In this paper, microwave-assisted ionic liquid method is applied to the preparation of cellulose/CaCO(3) hybrid nanocomposites in the alkali extraction cellulose using CaCl(2) and Na(2)CO(3) as starting reactants. The ionic liquid acts as the excellent solvent for absorbing microwave and the dissolution of cellulose, and the synthesis of cellulose/CaCO(3) nanocomposites. The influences of reaction parameters such as the cellulose concentration and the types of solvent on the products were investigated. The increasing cellulose concentration favored the growth of CaCO(3). The morphologies of CaCO(3) changed from polyhedral to cube to particle with increasing cellulose concentration. Moreover, the solvents had an effect on the shape and dispersion of CaCO(3). Cytotoxicity experiments demonstrated that the cellulose/CaCO(3) nanocomposites had good biocompatibility and could be a candidate for the biomedical applications.

Environmentally friendly microwave ionic liquids synthesis of hybrids from cellulose and AgX (X=Cl, Br).

The purpose of this article was to explore an environmentally friendly strategy to synthesis of biomass-based hybrids. Herein, microwave-assisted ionic liquids method was applied to fabricate the hybrids from cellulose and AgX (X=Cl, Br) using cellulose and AgNO3. The ionic liquids act simultaneously as a solvent, a microwave absorber, and a reactant. Ionic liquids provided Cl(-) or Br(-) to the synthesis of AgCl or AgBr crystals; thus no additional reactant is needed. The products are characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectrometry (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential thermal analysis (DTA). The cellulose-Ag/AgCl hybrid and cellulose-Ag/AgBr hybrid were also obtained by using cellulose-AgCl and cellulose-AgBr hybrids as precursors. This environmentally friendly microwave-assisted ionic liquids method is beneficial to the hybrids with high dispersion.