Identification of biomarkers of acne based on transcriptome analysis and combined with network pharmacology to explore the therapeutic mechanism of Jinhuang ointment.

The incidence of acne is on the rise due to unhealthy diet and living habits. Jinhuang ointment (JHO) is a classic prescription composed of 10 kinds of commonly used Chinese herbal medicine, which has been widely used in clinical prevention and treatment of skin inflammatory diseases since ancient times. However, the pharmacological mechanism and target of JHO are not clear. The acne microarray dataset was downloaded from gene expression omnibus database to identify differentially expressed genes (DEG). Immune infiltration was analyzed by CiberSort algorithm. HUB gene was identified by protein-protein interaction network. The gene expression omnibus dataset validates the biomarkers of acne with high diagnostic value. The potential active components and targets of JHO were obtained through Traditional Chinese Medicine Systems Pharmacology database, and the therapeutic targets were obtained by crossing with disease targets. R-packet is used for enrichment analysis. Molecular docking using Auto Dock Tools. A total of 202 DEGs were identified from 12 skin samples in the GSE6475. Immune infiltration analysis showed that there were a large number of macrophages and mast cells in acne skin. Gene set enrichment analysis analysis showed that DEGS was mainly involved in bacterial reaction, inflammatory reaction and so on. Six central genes and gene cluster modules were identified by Cytoscape software. A total of 185 JHO active components and 220 targets were obtained, of which 10 targets were potential targets for JHO in the treatment of acne. Kyoto encyclopedia of genes and genomes enrichment analysis showed that JHO treatment of acne was mainly related to Toll-like receptors, IL-17 and other signal pathways. The results of molecular docking showed that 5 active compounds in JHO had strong binding activity to the core protein receptor. IL-1 ß, CXCL8, toll-like receptor 2, CXCL2, LCN2, and secretory phosphoprotein 1 may be potential biomarkers for early diagnosis of acne. JHO active components may regulate skin cell metabolism and inflammatory response and improve cellular immune microenvironment by acting on core targets (CXCL8, ESR1, IL-1 ß, MMP1, MMP3, secretory phosphoprotein 1), thus achieving the purpose of treating acne. This is the result of the joint action of multiple targets and multiple pathways. It provides an idea for the development of a new combination of drugs for the treatment of acne.

MVIRA: A model based on Missing Value Imputation and Reliability Assessment for mortality risk prediction.

BACKGROUND: Mortality risk prediction is to predict whether a patient has the risk of death based on relevant diagnosis and treatment data. How to accurately predict patient mortality risk based on electronic health records (EHR) is currently a hot research topic in the healthcare field. In actual medical datasets, there are often many missing values, which can seriously interfere with the effect of model prediction. However, when missing values are interpolated, most existing methods do not take into account the fidelity or confidence of the interpolated values. Misestimation of missing variables can lead to modeling difficulties and performance degradation, while the reliability of the model may be compromised in clinical environments. MATERIALS AND METHODS: We propose a model based on Missing Value Imputation and Reliability Assessment for mortality risk prediction (MVIRA). The model uses a combination of variational autoencoder and recurrent neural networks to complete the interpolation of missing values and enhance the characterization ability of EHR data, thus improving the performance of mortality risk prediction. In addition, we also introduce the Monte Carlo Dropout method to calculate the uncertainty of the model prediction results and thus achieve the reliability assessment of the model. RESULTS: We perform performance validation of the model on the public datasets MIMIC-III and MIMIC-IV. The proposed model showed improved performance compared with competitive models in terms of overall specialties. CONCLUSION: The proposed model can effectively improve the accuracy of mortality risk prediction, and can help medical institutions assess the condition of patients.

A drug molecular classification model based on graph structure generation.

Molecular property prediction based on artificial intelligence technology has significant prospects in speeding up drug discovery and reducing drug discovery costs. Among them, molecular property prediction based on graph neural networks (GNNs) has received extensive attention in recent years. However, the existing graph neural networks still face the following challenges in node representation learning. First, the number of nodes increases exponentially with the expansion of the perception field, which limits the exploration ability of the model in the depth direction. Secondly, the large number of nodes in the perception field brings noise, which is not conducive to the model's representation learning of the key structures. Therefore, a graph neural network model based on structure generation is proposed in this paper. The model adopts the depth-first strategy to generate the key structures of the graph, to solve the problem of insufficient exploration ability of the graph neural network in the depth direction. A tendentious node selection method is designed to gradually select nodes and edges to generate the key structures of the graph, to solve the noise problem caused by the excessive number of nodes. In addition, the model skillfully realizes forward propagation and iterative optimization of structure generation by using an attention mechanism and random bias. Experimental results on public data sets show that the proposed model achieves better classification results than the existing best models.

Employee Stock Ownership Plans and Corporate Environmental Performance: Evidence from China.

In the context of corporate sustainability, studies on the role that managerial incentives play in improving corporate environmental performance have so far focused on incentives provided either to executives and senior managers or to plant managers. However, few studies have considered the role of employee incentives. Drawing on the opportunity provided by the China Securities Regulatory Commission in restarting employee stock ownership plans (ESOPs) in 2014, this paper investigates the impact of employee incentives on environmental performance of high-polluting enterprises. The results indicate that ESOPs are significantly positively related to corporate environmental performance. The positive effect is particularly pronounced in subsamples with weak free-riding problems, high human capital quality, and non-state-owned enterprises (non-SOEs). Further analysis reveals that ESOPs improve corporate environmental performance through enhancing productivity and green technology. Overall, this paper reveals the micro-mechanisms behind the actual effects of employee incentives on corporate environmental management, thus providing timely implications for high-polluting enterprises to improve environmental performance.

Inhibition of miRNA-155 Alleviates High Glucose-Induced Podocyte Inflammation by Targeting SIRT1 in Diabetic Mice.

OBJECTIVE: Microinflammation plays a crucial role in podocyte dysfunction in diabetic nephropathy, but its regulatory mechanism is still unclear. This study is aimed at discussing the mechanisms underlying the effect of miRNA-155 on podocyte injury to determine its potential as a therapeutic target. METHODS: Cultured immortalized mouse podocytes and diabetic KK-Ay mice models were treated with a miR-155 inhibitor. Western blotting, real-time PCR, ELISA, immunofluorescence, and Luciferase reporter assay were used to analyze markers of inflammation cytokines and podocyte injury. RESULTS: miRNA-155 was found to be highly expressed in serum and kidney tissue of mice with diabetic nephropathy and in cultured podocytes, accompanied by elevated levels of inflammatory factors. Inhibition of miRNA-155 can reduce proteinuria and ACR levels, diminish the secretion of inflammatory molecules, improve kidney function, inhibit podocyte foot fusion, and reverse renal pathological changes in diabetic nephropathy mice. Overexpression of miRNA-155 in vitro can increase inflammatory molecule production in podocytes and aggravates podocyte injury, while miRNA-155 inhibition suppresses inflammatory molecule production in podocytes and reduces podocyte injury. A luciferase assay confirmed that miRNA-155 could selectively bind to 3'-UTR of SIRT1, resulting in decreased SIRT1 expression. In addition, SIRT1 siRNA could offset SIRT1 upregulation and enhance inflammatory factor secretion in podocytes, induced by the miRNA-155 inhibitor. CONCLUSIONS: These findings strongly support the hypothesis that miRNA-155 inhibits podocyte inflammation and reduces podocyte injury through SIRT1 silencing. miRNA-155 suppression therapy may be useful for the management of diabetic nephropathy.

Characterization of Key Aroma Compounds and Construction of Flavor Base Module of Chinese Sweet Oranges.

Sweet orange flavor, with its refreshing, joyful and attractive aroma, is favored by the majority of consumers all over the world. However, the industry terminology between flavorists for flavor evaluation is a bit vague and not intuitive for customers. Therefore, the study focused on analysis of sweet orange aroma and establishment of base module of orange flavor. The approach to the research involves screening key aroma compounds, identifying the attributes aroma and building base module of sweet orange. The notes of sweet orange flavor were determined by GC-O olfaction and sensory evaluation. 25 key aroma compounds with OAV ≥ 1 were screened and divided into eight notes: citrus, fruity, fresh, green, peely, woody, fatty, floral. Partial least squares regression (PLSR) was used to further verify the corresponding relationship between the volatile substances and notes. Terpenes, esters, aldehydes and alcohols compounds can provide these notes. Based on the notes, 8 base modules of sweet orange were built by selecting and matching aroma ingredients. Through this study, beginners could be trained according to the 8 notes of base modules and flavorists can engage in dialogue with different raw material sourcing teams or providers.

Association between cognitive vulnerability to depression - dysfunctional attitudes and glycaemic control among in-patients with type 2 diabetes in a hospital in Beijing: a multivariate regression analysis.

This cross-sectional study aimed to investigate the relationship between glycosylated haemoglobin (HbA1c) and cognitive vulnerability to depression (dysfunctional attitudes) in patients with type 2 diabetes mellitus. A total of 245 valid records from June 2016 to December 2016 were collected from a hospital in Beijing. Participants were asked to complete four questionnaires (Dysfunctional Attitudes Scale, Automatic Thoughts Questionnaire, Zung Self-rating Depression Scale, and World Health Organization Quality of Life Instrument-Short Form) to assess mental health and quality of life. Multivariate regression analysis was conducted to determine the correlations between HbA1c, mental health, quality of life and other clinical variables. The results showed that dysfunctional attitudes were associated with HbA1c, with a standardized regression coefficient (ß) of .13 (p = .01), although 1 h C-peptide (ß = -.75, p < .0001) was the most significant predictor of HbA1c in the regression model. The results indicated that dysfunctional attitudes, as a cognitive vulnerability to depression, were a relevant factor in HbA1c, although further studies are needed to establish the nature of the connection between dysfunctional attitudes and glycaemic control in diabetes patients.

Graphene oxide quantum dot-sensitized porous titanium dioxide microsphere: Visible-light-driven photocatalyst based on energy band engineering.

We report a novel graphene oxide quantum dot (GOQD)-sensitized porous TiO2 microsphere for efficient photoelectric conversion. Electro-chemical analysis along with the Mott-Schottky equation reveals conductivity type and energy band structure of the two semiconductors. Based on their energy band structures, visible light-induced electrons can transfer from the p-type GOQD to the n-type TiO2. Enhanced photocurrent and photocatalytic activity in visible light further confirm the enhanced separation of electrons and holes in the nanocomposite.

["Re-evaluation upon suspected event" is an approach for post-marketing clinical study: lessons from adverse drug events related to Bupleuri Radix preparations].

We revisited the "Xiao Chaihu Decoction event (XCHDE)" occurred in late 1980s in Japan and the Bupleuri Radix related adverse drug reaction (ADR) reports in China After careful review, comparison, analysis and evaluation, we think the interstitial pneumonitis, drug induced Liver injury (DILI) and other severe adverse drug envents (ADEs) including death happened in Japan is probably results from multiple factors, including combinatory use of XCHDE with interferon, Kampo usage under modern medicine theory guidance, and use of XCHD on the basis of disease diagnosis instead of traditional Chinese syndrome complex differentiation. There are less ADE case reports related to XCHD preparation in China compared to Japan, mostly manifest with hypersensitivity responses of skin and perfuse perspiration. The symptoms of Radix Bupleuri injection related ADEs mainly manifest hypersensitivity-like response, 2 cases of intravenous infusion instead of intramuscular injection developed hypokalemia and renal failure. One case died from severe hypersensitivity shock. In Chinese literatures, there is no report of the interstitial pneumonitis and DILI associated with XCHDG in Japan. So far, there is no voluntary monitoring data and large sample clinical research data available. The author elaborated the classification of "reevaluation" and clarified "re-evaluation upon events" included the reaction to the suspected safety and efficacy events. Based on the current status of the clinical research on the Radix Bupleuri preparations, the author points out that post-marketing "re-evaluation upon suspected event" is not only a necessity of continuous evaluation of the safety, efficacy of drugs, it is also a necessity for providing objective clinical research data to share with the international and domestic drug administrations in the risk-benefit evaluation. It is also the unavoidable pathway to culture and push the excellent species and famous brands of TCM to the international market, in that it enhances the pharmaceutical manufactures the ability to control enterprise risk and eliminate the negative impact on traditional Chinese medicine. With the widely used and ADR report concentrated Radix Bupleuri injection as an example, the author provide a new approach to post-marketing clinical research.

[Determination of amphetamines in human urine using microwave extraction-gas chromatography].

A method has been developed for the determination of methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) in human urine using microwave extraction-gas chromatography(GC). To improve the extraction efficiency, experimental parameters of the extraction, including extraction solvent and its amount, pH value of the urine sample, extraction time and temperature were investigated. The optimal conditions were as follows: the pH value of urine sample at pH 12, cyclohexane as extraction solvent, extraction at 40 degrees C for 10 min. The average recoveries of MA, MDA and MDMA with this extraction method were 92.25%, 85.94% and 91.50%, the relative standard deviations were 5.5%, 5.5% and 6.1%(n = 5), and the limits of detection were 10, 20 and 20 ng/mL, respectively. Using this method, MA, MDA and MDMA need not be derivatized and can be separated from the matrix. The results indicate that the developed method is rapid, accurate and sensitive, and can be used for the simultaneous determination of MA, MDA and MDMA in urine samples.

[Determination of methamphetamine in human blood using microwave extraction-gas chromatography].

A method was developed for the determination of methamphetamine (MAM) in human blood using microwave extraction-gas chromatography (GC). To improve the extraction efficiency, experimental parameters on the extraction, including such as extraction solvent and its amount, pH value of blood sample, extraction time and temperature were investigated. Comparing with conventional liquid-liquid extraction method, the microwave extraction showed better efficiency under the optimal conditions. The optimal conditions were as follows: the pH of blood sample at 13, ethyl acetate as extraction solvent, extraction at 30 degrees C for 8 min. The average recovery of MAM with this extraction method was 81.4%, and the relative standard deviation was 6.4%. The limit of detection was 220 microg/L for MAM in the blood. Using this method, MAM need not be derivatized and can be separated from the matrix. The results indicate that the developed method is rapid, accurate and sensitive, and can be used for the determination of MAM in blood samples.