Effectiveness of Educational Interventions for Health Workers on Antibiotic Prescribing in Outpatient Settings in China: A Systematic Review and Meta-Analysis

Educational interventions are considered an important component of antibiotic stewardship, but their effect has not been systematically evaluated in outpatient settings in China. This research aims to evaluate the effectiveness of educational interventions for health workers on antibiotic prescribing rates in Chinese outpatient settings. Eight databases were searched for relevant randomized clinical trials, non-randomized trials, controlled before-after studies and interrupted time-series studies from January 2001 to July 2021. A total of 16 studies were included in the systematic review and 12 in the meta-analysis. The results showed that educational interventions overall reduced the antibiotic prescription rate significantly (relative risk, RR 0.72, 95% confidence interval, CI 0.61 to 0.84). Subgroup analysis demonstrated that certain features of education interventions had a significant effect on antibiotic prescription rate reduction: (1) combined with compulsory administrative regulations (RR With: 0.65 vs. Without: 0.78); (2) combined with financial incentives (RR With: 0.51 vs. Without: 0.77). Educational interventions can also significantly reduce antibiotic injection rates (RR 0.83, 95% CI 0.74 to 0.94) and the inappropriate use of antibiotics (RR 0.61, 95% CI 0.51 to 0.73). The limited number of high-quality studies limits the validity and reliability of the results. More high-quality educational interventions targeting the reduction of antibiotic prescribing rates are needed

Proteomics and network pharmacology of Ganshu Nuodan capsules in the prevention of alcoholic liver disease

IntroductionGanshu Nuodan is a liver-protecting dietary supplement composed of Ganoderma lucidum (G. lucidum) spore powder, Pueraria montana (Lour.) Merr. (P. montana), Salvia miltiorrhiza Bunge (S. miltiorrhiza) and Astragalus membranaceus (Fisch.) Bunge. (A. membranaceus). However, its pharmacodynamic material basis and mechanism of action remain unknown.MethodsA mouse model of acute alcohol liver disease (ALD) induced by intragastric administration of 50% alcohol was used to evaluate the hepatoprotective effect of Ganshu Nuodan. The chemical constituents of Ganshu Nuodan were comprehensively identified by UPLC-QTOF/MS, and then its pharmacodynamic material basis and potential mechanism of action were explored by proteomics and network pharmacology.ResultsGanshu Nuodan could ameliorate acute ALD, which is mainly manifested in the significant reduction of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and malondialdehyde (MDA) content in liver and the remarkably increase of glutathione (GSH) content and superoxide dismutase (SOD) activity in liver. Totally 76 chemical constituents were identified from Ganshu Nuodan by UPLC-QTOF/MS, including 21 quinones, 18 flavonoids, 11 organic acids, 7 terpenoids, 5 ketones, 4 sterols, 3 coumarins and 7 others. Three key signaling pathways were identified via proteomics studies, namely Arachidonic acid metabolism, Retinol metabolism, and HIF-1 signaling pathway respectively. Combined with network pharmacology and molecular docking, six key targets were subsequently obtained, including Ephx2, Lta4h, Map2k1, Stat3, Mtor and Dgat1. Finally, these six key targets and their related components were verified by molecular docking, which could explain the material basis of the hepatoprotective effect of Ganshu Nuodan.ConclusionGanshu Nuodan can protect acute alcohol-induced liver injury in mice by inhibiting oxidative stress, lipid accumulation and apoptosis. Our study provides a scientific basis for the hepatoprotective effect of Ganshu Nuodan in acute ALD mice and supports its traditional application

P_VggNet: A convolutional neural network (CNN) with pixel-based attention map.

Attention maps have been fused in the VggNet structure (EAC-Net) [1] and have shown significant improvement compared to that of the VggNet structure. However, in [1], E-Net was designed based on the facial action unit (AU) center and for facial AU detection only. Thus, for the use of attention maps in every image type, this paper proposed a new convolutional neural network (CNN) structure, P_VggNet, comprising the following parts: P_Net and VggNet with 16 layers (VggNet-16). The generation approach of P_Net was designed, and the P_VggNet structure was proposed. To prove the efficiency of P_VggNet, we designed two experiments, which indicated that P_VggNet could more efficiently extract image features than VggNet-16

LINC00162 participates in the pathogenesis of diabetic nephropathy via modulating the miR-383/HDAC9 signalling pathway

AbstractDiabetic nephropathy (DN) is a common chronic complication of diabetes. In this study, we aimed to explore the potential role of lncRNA LINC-00162 in the pathogenic process of DN. LncRNA microarray analysis, real-time PCR, IHC computational analysis and luciferase assay were performed to explore the regulatory relationship among LINC00162, miR-383 and HDAC9. There was an obvious difference between T2D + DN and T2D − DN patients in their levels of eGRF and albuminuria. A significant difference was observed between T2D + DN and T2D − DN groups in terms of their LINC00162 expression. In particular, LINC00162 and HDAC9 were highly expressed, while miR-383 was lowly expressed in tissues derived from the T2D + DN group compared with those in tissues derived from the T2D − DN group. MiR-383 was able to bind to LINC00162, while HDAC9 was a direct downstream target of miR-383 with a complementary miR-383 binding site located in the 3′ UTR of HDAC9. LINC00162 reduced miR-383 expression and further up-regulated HDAC9 expression, while miR-383 mimics reduced HDAC9 expression under a dose-dependent manner. In summary, we suggested for the first time that down-regulation of LINC00162 was associated with the development of DN in T2D via the up-regulation of miR-383 expression and reduction of HDAC9 expression

Screening and identification of biomarkers in ascites related to intrinsic chemoresistance of serous epithelial ovarian cancers.

OBJECTIVE:The ability to predict responses to chemotherapy for serous epithelial ovarian cancer (EOC) would be valuable since intrinsically chemoresistant EOC patients (persistent or recurrent disease within 6 months) gain little benefit from standard chemotherapy. The aim of this study was to screen and identify distinctive biomarkers in ascites of serous EOC associated with intrinsic chemoresistance. METHODS:Protein samples from ascites of 12 chemosensitive and 7 intrinsically chemoresistant serous EOC patients were analyzed using two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS). Furthermore, the identified proteins were validated by ELISA in ascites samples from 19 chemosensitive and 9 intrinsically chemoresistant EOC patients. RESULTS:The number of spots detected in all 2-D DIGE gels ranged from 1523-1711 using DeCyder software analysis. Thirty-four spots were differentially expressed based on the criteria of an average ratio of more than 1.5 and a student t-test P value <0.05. After MALDI-TOF/TOF MS analysis, 11 differentially expressed proteins, including 3 up-regulated and 8 down-regulated proteins, in ascites of chemoresistant tumors were successfully identified. Of the four selected proteins (ceruloplasmin, apoliprotein A-IV, transthyretin and haptoglobin) in ascites tested by ELISA, only ceruloplasmin was present at significantly different levels between the chemoresistant and chemosensitive ascites samples with average concentrations of 192.2 µg/ml and 157.5 µg/ml, respectively (P = 0.001). CONCLUSION:The significantly up-regulated level of ceruloplasmin in the ascites fluid of intrinsic chemoresistant serous EOC patients suggests its potential as a prognostic biomarker for responses to chemotherapy. This finding prompts further investigation with a larger study in order to validate the clinical utility of ceruloplasmin

Differentially expressed proteins between chemosensitive and chemoresistant ovarian cancer ascites identified by MALDI-TOF/TOF MS.

a<p>Spot no. assigned by DeCyder 2-D Differential Analysis Software V6.0. corresponding to the DIGE image in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051256#pone-0051256-g001" target="_blank">Figure 1</a>.</p>b<p>Decreased or increased ratio of protein in ascites of intrinsic chemoresistant ovarian cancer compared to chemosensitive ones; “–” indicates down-regulation of protein in ascites.</p>c<p>Accession no. from NCBInr database.</p>d<p>Mascot scores greater than 40 were considered significant.</p>e<p>Protein function mainly categorized according to MeSH Tree Structure.</p>f<p>Alterations in the serum level may indicate: occurrence, tumor progression, response to therapy or prognosis for some malignancy reported in the literature.</p

Clinical characteristics of study subjects.

*<p>Resistance: intrinsically chemoresistant tumors were defined as those with persistent or recurrent disease within 6 months after the initiation of first-line platinum-based combination chemotherapy. Sensitive: chemosensitive tumors were classified as those with a complete response to chemotherapy and a platinum-free interval of >6 months.</p>**<p>Paclitaxel was changed to doxepaclitaxel due to grade III neurotoxicity.</p>***<p>Carboplatin was changed to cisplatin due to grade III neutropenia.</p

Comparison of survival between chemosensitive and intrinsic chemoresistant serous EOC patients.

<p>A significant difference (<i>P</i>  =  0.007) was observed in survival, which favored patients with chemosensitive tumors.</p

(top) Proteomic analysis of ascites by 2D-DIGE.

<p>A representative 2D-DIGE image (merged image) showing the protein profile of ascites of chemosensitive and chemoresistant ovarian cancer patients labeled with Cy5 (red spots) and Cy3 (green spots), respectively, with an internal standard labeled with Cy2. IPG strips (24 cm, pH 4-7) were used for IEF prior to standard SDS-PAGE (12.5% polyacrylamide) for the second dimension. The molecular weight range in the vertical dimension is approx from 150 to 10 kD. Proteins identified as differentially expressed are indicated with yellow arrows with assigned numbers from the DeCyder analysis. The numbers in the figure correspond to those presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051256#pone-0051256-t002" target="_blank">Table 2</a>; (bottom) MALDI–TOF–MS mass spectrum of spot 1543 identified as ceruloplasmin according to the matched peaks.</p

Concentrations of proteins in ascites of intrinsically chemoresistant and chemosensitive EOC.

*<p>Apo-AIV, apoliprotein A-IV; CP, ceruloplasmin; HB, haptoglobin; TTR, transthyretin.</p