Efficacy and safety of fenofibrate add-on therapy in patients with primary biliary cholangitis refractory to ursodeoxycholic acid: A retrospective study and updated meta-analysis.

Background: Ursodeoxycholic acid (UDCA) is currently used for the treatment of primary biliary cholangitis (PBC), but some people do not respond well to UDCA. It reported that the combination of fenofibrate and UDCA can improve the clinical indices in these patients. However, more high-quality evidence is needed to improve guideline recommendations. Methods: Through an updated meta-analysis, studies included were valued by the Cochrane Evaluation Manual and Robins-I. Biochemical and clinical indicator changes in UDCA-refractory PBC patients receiving combination therapy were analyzed by Revman 5.42. Then, we explored the influence of fenofibrate dose and the effectiveness and safety of long-term application by retrospective cohort study. Results: Our meta-analysis included nine publications with a total of 389 patients, including 216 treated with UDCA alone and 173 who received combination therapy. The meta-analysis showed that combination therapy was more effective than UDCA monotherapy in decreasing biochemical parameters, such as ALP, GGT, IgM, and TG. However, the occurrence of pruritus and adverse events was slightly higher with combination therapy than with UDCA monotherapy. A total of 156 patients were included in our cohort study: 68 patients underwent UDCA monotherapy, and 88 patients underwent combination therapy. Among UDCA-refractory patients, fenofibrate add-on therapy significantly improved the ALP normalization rate. Conclusion: The combination of fenofibrate and UDCA can decrease biochemical parameters, of UDCA-refractory PBC patient. Furthermore, the efficacy and safety of long-term combination therapy were also confirmed in our cohort study.

Quantitative analysis and prediction of urban heat island intensity on urban-rural gradient: A case study of Shanghai.

Urbanization causes enormous land use/land cover (LULC) changes, which have become significant drivers of land surface temperature (LST) change in rapidly urbanizing city, and the changes in LULC subsequently increase the LST to form urban heat island (UHI). This paper first identified the spatial distribution pattern of the LULC changes and surface urban heat island intensity (SUHII) in the study area in recent 20 years based on Landsat TM/OLI data. And later, the relationship between the distribution of impervious surface (IS) and vegetable coverage (VC) and SUHII was analyzed quantitatively. Then, the land cover and land surface temperature (LST) in Shanghai in 2027 under three development modes were simulated and predicted based on FLUS model and geospatial analysis. The results showed that (1) Regional land cover and LST had obvious differences in gradient distribution from urban to rural areas, and the outer ring road (Ring3) was an obvious dividing line; (2) the proportion of IS and VC were significantly positively (|R| > 0.695) and negatively (|R| > 0.328) correlated with LST; (3) under the three different scenario development models, the ecological space protection model effectively regulated the SUHII, which was 15.91% less than the SUHII in 2017 (34% inside Ring3 and 14% outside Ring3). The results could provide a reference for the rational allocation of urban land and landscape optimization in reducing SUHII` in typical urbanized areas.

Comprehensive investigation of alternative splicing and development of a prognostic risk score for prostate cancer based on six-gene signatures.

Purpose: To systematically document alternative splicing profiles of prostate cancer in relatively large populations in order to construct a prognostic predictors model for prostate cancer. Methods: Splicing data and clinical information of 495 prostate cancer patients were obtained from The Cancer Genome Atlas (TCGA). The SpliceSeq database was used to extract information regarding splicing events. Multiple bioinformatic tools were used for functional and pathway enrichment analysis as well as for construction of gene interaction networks. Candidate gene expression profiles were verified with clinical samples using QRT-PCR. Results: We detected a total of 44070 alternative splicing events of 10381 genes in prostate cancer. 7 and 14 KEGG pathways were enriched and were associated with overall and recurrence-free survival, respectively. The expression of 396 genes among the 1526 overall survival genes associated alternative splicing events were associated with overall survival. The expression of 483 genes among the 1916 recurrence-free survival genes associated alternative splicing events were associated with recurrence-free survival. Lastly, we constructed the prognosis risk score system based on the expression profiles of six-gene signatures which in combination had an AUC of 0.941 for overall survival associated alternative splicing events, followed by overall survival associated gene expressions with an AUC of 0.794, a recurrence-free survival associated gene expression with an AUC of 0.752 and recurrence-free survival associated alternative splicing events with an AUC of 0.735, indicating its strong ability to predict patient outcome. The expression profile of the six genes was also confirmed in different prostate cell lines and clinic samples. Conclusion: Our comprehensive investigation of alternative splicing not only provided insight into the biological pathways of alternative splicing involved in the development of prostate cancer but also revealed new potential biomarkers for prognosticating as well as novel therapeutic targets for development of prostate cancer treatment.

Effects of two enzyme extracts of Aspergillus niger on green tea aromas.

Green tea was investigated in terms of its aroma changes induced by two enzyme extracts of Aspergillus niger, i.e., crude enzyme extracted from fermentation using tea stalk medium (CETSM) and crude enzyme yielded in potato dextrose medium. The result showed that the former had significant effects on sensory indexes and volatile constituents, with significant increases in toasty and mushroom notes, while the latter had little influence on the aforementioned indexes. In addition, the volatile constituents were significantly affected; in particular, the contents of cis-3-hexenol, 1-octen-3-ol, eucalyptol, hexanol, and benzaldehyde increased. Furthermore, gas chromatography-olfactometry (GC-O) analysis showed that an increase in 1-octen-3-ol strengthened the mushroom note. These results indicate that CETSM contains some novel enzymes that can modify the aroma profile of green tea. This study also provides valuable information and suggestions to use fermented enzymes to modify food aromas.

Joint Design of Excitation k-Space Trajectory and RF Pulse for Small-Tip 3D Tailored Excitation in MRI.

We propose a new method for the joint design of k-space trajectory and RF pulse in 3D small-tip tailored excitation. Designing time-varying RF and gradient waveforms for a desired 3D target excitation pattern in MRI poses a non-linear, non-convex, constrained optimization problem with relatively large problem size that is difficult to solve directly. Existing joint pulse design approaches are therefore typically restricted to predefined trajectory types such as EPI or stack-of-spirals that intrinsically satisfy the gradient maximum and slew rate constraints and reduce the problem size (dimensionality) dramatically, but lead to suboptimal excitation accuracy for a given pulse duration. Here we use a 2nd-order B-spline basis that can be fitted to an arbitrary k-space trajectory, and allows the gradient constraints to be implemented efficiently. We show that this allows the joint optimization problem to be solved with quite general k-space trajectories. Starting from an arbitrary initial trajectory, we first approximate the trajectory using B-spline basis, and then optimize the corresponding coefficients. We evaluate our method in simulation using four different k-space initializations: stack-of-spirals, SPINS, KT-points, and a new method based on KT-points. In all cases, our approach leads to substantial improvement in excitation accuracy for a given pulse duration. We also validated our method for inner-volume excitation using phantom experiments. The computation is fast enough for online applications.

Intraneobladder Hem-o-Lok Migration with Stone Formation after Orthotopic Neobladder Cystectomy.

Introduction. Laparoscopic and robot-assisted laparoscopic surgery are widely performed in urology field, so Hem-o-Lok clips are thus extensively used in the laparoscopic procedures. We describe the first case of Hem-o-Lok clip which migrated into the neobladder with calculus formation 26 months after laparoscopic orthotopic neobladder cystectomy, which causes symptoms of gross hematuria and frequent urination. Case Presentation. A 57-year-old man with T2a muscle invasive bladder cancer underwent laparoscopic orthotopic sigmoid neobladder reconstruction after cystectomy which was complicated by intestinal anastomosis leak and peritoneal abscess requiring transverse colostomy and drainage 15 days postoperatively. Twenty-six months after cystectomy, he complained of gross hematuria and frequent urination. Computerized tomography and plain pelvic X-ray revealed a stone measuring approximately 2.8 cm in diameter in the neobladder. During cystoscopy, a closed whitish Hem-o-Lok clip was seen in the center of the calculi. No anastomotic leak or neoplasm was found during cystoscopy. Conclusion. Hem-o-Lok clip migration into the bladder after laparoscopic orthotopic neobladder cystectomy is a rare complication; the first reported case in the literature. To prevent Hem-o-Lok clip migration, it is recommended to avoid extensive use of Hem-o-Lok clip close to anastomosis site, and any loose Hem-o-Lok clip should be retrieved before closure.

Development of an ionic liquid-based dispersive liquid-liquid micro-extraction method for the determination of phthalate esters in water samples.

Ionic liquid-based dispersive liquid-liquid micro-extraction (IL-DLLME) was coupled with high-performance liquid chromatography-ultraviolet (HPLC-UV) for the determination of four phthalate esters, including butyl benzyl phthalate, di-n-butyl phthalate, dicyclohexyl phthalate and bis(2-ethylhexyl) phthalate in water samples. The mixture of ionic liquid (IL) and dispersive solvent was rapidly injected into 10 mL aqueous sample. Then, IL phase was separated by centrifugation and was determined by high-performance liquid chromatography-ultraviolet. The factors influencing the extraction efficiency, such as type and volume of IL, disperse solvent, extraction time, centrifuging time and ionic strength, were investigated and optimized. Under the optimized conditions, the extraction recoveries by the proposed ionic liquid-based dispersive liquid-liquid micro-extraction for the four phthalates ranged from 83.0 to 91.7%. The relative standard deviations were between 7.8 and 15%. The limits of quantification for four phthalates were between 10.6 and 28.5 µg/L. The proposed method was successfully applied for the analysis of PAEs in tap, lake and treated wastewater samples.

An application of a service-oriented system to support array annotation in custom chip design for epigenomic analysis.

We present the implementation of an application using caGrid, which is the service-oriented Grid software infrastructure of the NCI cancer Biomedical Informatics Grid (caBIG), to support design and analysis of custom microarray experiments in the study of epigenetic alterations in cancer. The design and execution of these experiments requires synthesis of information from multiple data types and datasets. In our implementation, each data source is implemented as a caGrid Data Service, and analytical resources are wrapped as caGrid Analytical Services. This service-based implementation has several advantages. A backend resource can be modified or upgraded, without needing to change other components in the application. A remote resource can be added easily, since resources are not required to be collected in a centralized infrastructure.

High-yield conversion of (R)-2-octanol from the corresponding racemate by stereoinversion using Candida rugosa.

Whole cells of Candida rugosa catalyzed the conversion of (R)-2-octanol from the corresponding racemate with the optical purity of 97% e.e. and yield of 92% in 10 h. The product was formed through a stereoinversion involving enantioselective oxidation and asymmetric reduction with 2-octanone as the intermediate.

Monitoring gene expression profile changes in bladder transitional cell carcinoma using cDNA microarray.

PURPOSE: Differential gene expression profiles between normal bladder mucosas and bladder transitional cell carcinomas TCC were detected. MATERIALS AND METHODS: cDNA microarrays were prepared by spotting PCR products of 12,800 human genes onto specially treated glass slides. The cDNA probes were prepared by labeling normal bladder mucosa mRNA and TCC tissue mRNA with Cy3-dUTP and Cy5-dUTP respectively through reverse transcription. The arrays were then hybridized against the cDNA probe mixture and the fluorescent signals were scanned. The ratios of Cy5/Cy3 were computed. Northern analysis was used to confirm the results of microarray hybridization. RESULTS: Eighty-three genes (0.65%), whose ratios of Cy5/Cy3 were greater than 4.0 or less than 0.25, were screened out after 10 groups of hybridization. In the cancerous tissues 28 of them showed higher expression and 55 lower. Twenty-three genes are unregistered in GenBank. These differentially expressed genes are always involved in the physiological processes such as signal transduction, apoptosis and cell cycle, etc. CONCLUSIONS: This technique provides a powerful method for quantitative analysis of the expression levels of thousands of genes in parallel, and is used to identify genes involved in TCC carcinogenesis. The data obtained by this means are comparable to those obtained by other methods. Using cDNA microarrays to define alterations in gene expression associated with a specific cancer may be an efficient way to uncover the clues to specific molecular derangements that account for its pathogenesis and thus identify potential targets for therapeutic intervention.