Histological response to combination therapy with nucleos(t)ide analogs and peginterferon alpha in treatment-naïve chronic hepatitis B patients.

Although nucleos(t)ide analog (NA) monotherapy is effective in hepatitis B virus suppression and fibrosis regression, serological response rates are not satisfactory. Studies assessing the benefits of combination therapy with NAs and peginterferon alpha (PegIFNα) in patients with chronic hepatitis B (CHB) have produced conflicting results and mainly focused on serological outcomes. Histological changes in response to combination therapy have not been evaluated in real-world practice. This study aimed to evaluate the histological changes in response to NA-PegIFNα combination therapy in CHB patients and to comprehensively compare the efficacy of NA-PegIFNα combination therapy and NA monotherapy. We conducted a retrospective analysis of data from 40 CHB patients who underwent either NA-PegIFNα combination therapy or NA monotherapy. Changes in histology at 48 weeks after treatment initiation were evaluated. Serological characteristics were also analysed and compared between the NA-PegIFNα combination therapy and NA monotherapy groups and between histological responders and nonresponders. Compared to baseline biopsies, both fibrosis staging and necroinflammatory grading scores were significantly lower in the second biopsies examined post-treatment in both groups. Nearly all patients experienced a reduction in inflammation (87.5% in both groups), but there was a subgroup of patients who exhibited either no significant improvement or fibrosis progression (33.3% and 31.2% in the NA monotherapy and NA-PegIFNα combination therapy groups, respectively). Nearly, all patients achieved ALT normalization and sustained virological response (SVR) after 48 weeks of antiviral treatment. Approximately one-third of individuals (36.8% and 30% in the two groups, respectively) achieved HBeAg loss at 48 weeks after treatment initiation. Although there were no significant differences in overall rates of histological, biochemical, virological and serological responses between the two groups, an earlier virological response and a higher cumulative SVR rate over time were observed during long-term follow-up in patients treated with NA-PegIFNα combination therapy (P = 0.0129). Trends of more rapid HBeAg loss and a higher cumulative HBeAg loss rate throughout long-term follow-up were also observed but were not statistically significant. The ALT normalization rates at 24 and 48 weeks after treatment initiation were associated with the histological response. Significant regression of fibrosis and resolution of necroinflammation were induced with either NA-PegIFNα combination therapy or NA monotherapy. Significant biochemical, virological and serological responses were observed in both groups, and the response rates at 48 weeks were similar in the two groups. Over time during long-term follow-up, the virological and serological responses were faster and superior following the combination regimen.

[A meta-analysis of diammonium glycyrrhizinate enteric-coated capsules versus diammonium glycyrrihizinate in patients with chronic viral hepatitis].

OBJECTIVE: To systematically evaluate the efficacy and safety of diammonium glycyrrhizinate enteric-coated capsules versus diammonium glycyrrihizinate in patients with chronic viral hepatitis. METHODS: The Chinese Biomedical Literature Database (CBM on CD-ROM) and the China Academic Journals Full-Text Database (Chinese National Knowledge Infrastructure, CNKI) were searched for randomized controlled trials (RCTs) that compared the efficacy and safety of diammonium glycyrrhizinate entetic-coated capsules versus diammonium glycyrrihizinate in treatment (less than 2 months) of chronic viral hepatitis published between 2005 and 2012. A meta-analysis was performed on the selected RCTs to determine the effects on alanine aminotransferase (ALT) normalization, serum levels of ALT, aspartate aminotransferase (AST), total bilirubin (TBil) and albumin, as well as rates of adverse reactions. RESULTS: Nine RCTs, involving 687 patients, were included in the meta-analysis. Compared to the patients treated with diammonium glycyrrihizinate, the patient treated with diammonium glycyrrhizinate enteric-coated capsules had a significantly better recovery rate of ALT (relative risk (RR) =4.15, 95% confidence interval (CI):1.55 to 11.15, P less than 0.01) and significantly more robust decreases in ALT (weighted mean difference (WMD) = -32.75, 95% CI:-46.67 to-18.83, P less than 0.01) and AST (WMD = -12.70, 95% CI:-21.13 to-4.27, P less than 0.01). In contrast, the patients treated with diammonium glycyrrihizinate showed more robust improvements in the TBil level (WMD = -0.74, 95% CI:3.98 to 2.49, P =0.653) and albumin (WMD =1.03, 95% CI:-1.03 to 3.09, P =0.326), but the differences did not reach the threshold for statistical significance (P less than 0.05). Only four adverse reactions were reported, all of which were related to the lipid complex nature of the diammonium glycyrrhizin enteric-coated capsules and were mild, including dry mouth, dizziness and mild gastrointestinal discomfort and reactions. CONCLUSION: Diammonium glycyrrhizinate enteric-coated capsules elicited superior anti-inflammatory and liver protection effects than diammonium glycyrrihizinate, and produced only mild side effects that are tolerable to the patients.

BTA Deep Hole Vibration Drilling for Nickel-Based Alloys: Cooling Patterns and Cutter Tooth Wear Mechanisms.

The high cutting temperature and poor thermal diffusion efficiency of nickel-based alloys during deep hole machining have become technical challenges in the hole machining field. In this paper, a finite element simulation model of Inconel-718 BTA ordinary drilling and vibration drilling processes was established by using Deform-3D finite element simulation software. The variations in the temperatures of the tool teeth and the workpiece at different positions of the nickel-based alloy under ordinary drilling and vibration drilling were investigated. Additionally, the wear pattern of each tool tooth under the two drilling methods was further analyzed by building an experimental platform for workpiece temperature detection, which reveals the wear and cooling mechanism of nickel-based alloy BTA deep hole drilling. The results show that the average temperatures of the external, intermediate, and central teeth were reduced by 18.1%, 21.1%, and 17.8%, respectively, during vibration drilling. In addition, the workpiece hole wall and hole bottom temperatures were reduced by 5.7% and 4.6%, respectively. To conclude, the experimental tests were consistent with the simulated temperature trends. BTA vibration drilling optimizes the heat exchange conditions between the cutter teeth and the workpiece during the drilling of nickel-based alloys, which effectively reduces the cutting temperature and, thus, improves the wear resistance of the cutter teeth.

Spectroscopic studies of solutes in aqueous solution.

Absorption and fluorescence characteristics of aqueous solutions of salts, sugars, and amino acids were studied using UV-vis spectroscopy and spectrofluorometry. Motivation stemmed from unanticipated absorption spectral and fluorescence features of the "exclusion zone" seen adjacent to various hydrophilic surfaces. Those features implied a structure distinct from that of bulk water (Adv. Colloid Interface Sci. 2006, 127, 19). Absorption peaks at approximately 270 nm similar to those observed in the exclusion zone were seen in solutions of the following substances: salts, Nafion 117 solution/film, l-lysine, d-alanine, d-glucose and sucrose. To determine the fate of the absorbed energy, we studied the fluorescence properties of these solutions. The salts showed fluorescence emission around 480-490 nm under different excitation wavelengths. The fluorescence intensity of LiCl was higher than NaCl, which was in turn higher than KCl-the same ordering as the absorption intensities. Fluorescence of Nafion 117 solution/film, l-lysine, d-alanine, d-glucose and sucrose were observed as well, with multiple excitation wavelengths. Hence, at least some of the absorbed energy is released as fluorescence. The results show features closely similar to those observed in the exclusion zone, implying that the aqueous region around the solutes resembles the aqueous zone adjacent to hydrophilic surfaces. Both may be more extensively ordered than previously thought.

The Earliest Chinese Proto-Porcelain Excavated from Kiln Sites: An Elemental Analysis.

In June 2012, the Piaoshan kiln site was excavated in Huzhou, Zhejiang Province, which hitherto proved to be the earliest known Chinese proto-porcelain kiln. Judging from the decorative patterns of unearthed impressed stoneware and proto-porcelain sherds, the site was determined to date to the late Xia (c. 2070-c. 1600 BC), the first dynasty of China. Here, we report on proton-induced X-ray emission analyses of 118 proto-porcelain and 35 impressed stoneware sherds from Piaoshan and five subsequent kiln sites in the vicinity. Using principal components analysis on the major chemical compositions, we reveal the relationships between impressed stoneware and proto-porcelain samples from the six kiln sites. The sherds from different sites have distinctive chemical profiles. The results indicate that the raw materials were procured locally. We find a developmental tendency for early glazes towards mature calcium-based glaze. It is most likely that woody plant ashes with increased calcia-potash ratios were applied to the formula.

Long-range forces extending from polymer-gel surfaces.

Aqueous suspensions of microspheres were infused around gels of varying composition. The solutes were excluded from zones on the order of 100 microm from the gel surface. We present evidence that this finding is not an artifact, and that solute-repulsion forces exist at distances far greater than conventional theory predicts. The observations imply that solutes may interact over an unexpectedly long range.