Publications by authors named "Zhiwei Bao"

16 Publications

  • Page 1 of 1

Identification of Diagnostic Markers for Major Depressive Disorder Using Machine Learning Methods.

Front Neurosci 2021 18;15:645998. Epub 2021 Jun 18.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Major depressive disorder (MDD) is a global health challenge that impacts the quality of patients' lives severely. The disorder can manifest in many forms with different combinations of symptoms, which makes its clinical diagnosis difficult. Robust biomarkers are greatly needed to improve diagnosis and to understand the etiology of the disease. The main purpose of this study was to create a predictive model for MDD diagnosis based on peripheral blood transcriptomes.

Materials And Methods: We collected nine RNA expression datasets for MDD patients and healthy samples from the Gene Expression Omnibus database. After a series of quality control and heterogeneity tests, 302 samples from six studies were deemed suitable for the study. R package "MetaOmics" was applied for systematic meta-analysis of genome-wide expression data. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic effectiveness of individual genes. To obtain a better diagnostic model, we also adopted the support vector machine (SVM), random forest (RF), k-nearest neighbors (kNN), and naive Bayesian (NB) tools for modeling, with the RF method being used for feature selection.

Results: Our analysis revealed six differentially expressed genes (, , , , , and ) with a false discovery rate (FDR) < 0.05 between MDD patients and control subjects. We then evaluated the diagnostic ability of these genes individually. With single gene prediction, we achieved a corresponding area under the curve (AUC) value of 0.63 ± 0.04, 0.67 ± 0.07, 0.70 ± 0.11, 0.64 ± 0.08, 0.68 ± 0.07, and 0.62 ± 0.09, respectively, for these genes. Next, we constructed the classifiers of SVM, RF, kNN, and NB with an AUC of 0.84 ± 0.09, 0.81 ± 0.10, 0.73 ± 0.11, and 0.83 ± 0.09, respectively, in validation datasets, suggesting that the SVM classifier might be superior for constructing an MDD diagnostic model. The final SVM classifier including 70 feature genes was capable of distinguishing MDD samples from healthy controls and yielded an AUC of 0.78 in an independent dataset.

Conclusion: This study provides new insights into potential biomarkers through meta-analysis of GEO data. Constructing different machine learning models based on these biomarkers could be a valuable approach for diagnosing MDD in clinical practice.
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http://dx.doi.org/10.3389/fnins.2021.645998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249859PMC
June 2021

Sub-chronic exposure to antibiotics doxycycline, oxytetracycline or florfenicol impacts gut barrier and induces gut microbiota dysbiosis in adult zebrafish (Daino rerio).

Ecotoxicol Environ Saf 2021 Sep 29;221:112464. Epub 2021 Jun 29.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Antibiotics are widely used in the treatment of bacterial infections and as food additives in the livestock industry. The wide usage of antibiotics causes residues in animal products, like milk, eggs and meat. A number of studies have reported that antibiotic residues exist at high concentrations in watercourses around the world. Doxycycline (DH), oxytetracycline (OTCC) and florfenicol (FF) are the three most commonly used veterinary antibiotics in China. However, studies of the toxic effects of DH, OTCC and FF are limited. In this study, six-moth-old healthy male adult zebrafish were exposed to 0, 10, 30, 100 μg/L DH, OTCC or FF for 21 days. After exposure, some biochemical parameters changed significantly, including total cholesterol (TC), triglyceride (TG), pyruvate and acid phosphatase (ACP). In addition, mucus secretion in the gut decreased and the transcription of related genes also decreased significantly. Moreover, the composition of microbiota in the gut changed significantly. DH, OTCC and FF exposure caused the decrease of diversity of gut microbiota. The relative abundance of Proteobacteria increased significantly after OTCC and FF exposure and Fusobacteria decreased in all antibiotic-treated groups. Further functional prediction analysis also suggested changes in gut microbiota in the OTCC and FF-treated groups, especially those linked to metabolism. To support this idea, we confirmed that some glycolipid related genes also increased significantly in the liver of adult zebrafish after antibiotic exposure. According to these results, DH, OTCC or FF exposure could cause the gut microbiota dysbiosis and dysfunction, and hepatic metabolic disorder in adult male zebrafish.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112464DOI Listing
September 2021

Embryonic toxicity of epoxiconazole exposure to the early life stage of zebrafish.

Sci Total Environ 2021 Jul 16;778:146407. Epub 2021 Mar 16.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Epoxiconazole (EPX), as a broad-spectrum triazole fungicide, is widely used in agriculture to resist pests and diseases, while it may have potential toxicity to non-target organisms. In the present study, early developmental stage zebrafish were used as the subject organisms to assess the toxicity of EPX, and the possible mechanism of toxicity was also discussed by biochemical and transcriptomic analysis. Through embryo toxicity test, we had made it clear that the 96 h LC of embryo was 7.204 mg/L, and acute exposure to EPX effected hatching rate, heartbeats, body length and even morphological defects. Then, by being exposed to EPX for 7 days at concentrations of 175 (1/40 LC), 350 (1/20 LC) and 700 (1/10 LC), biochemical parameters were affected, mainly manifested as increase of the triglyceride (TG) level and decrease of glucose content. Correspondingly, the transcription of genes related of glucose metabolism, lipid metabolism and cholesterol metabolism were also affected significantly in larval zebrafish. Moreover, some pathways, including lipid metabolism, glucose metabolism and amino acid metabolism were affected through transcriptome sequencing analysis in the larval zebrafish. Further data analysis based on the sequencing, EPX exposure also affected the expression of genes related to cell apoptosis. We further conformed that the bright fluorescence on the liver and bright spots near the liver by acridine orange staining. In addition, the mRNA levels of apoptosis related genes were also significantly affected in the EPX exposed larval zebrafish. Taken together, the work could provide an insight into toxic effects of EPX on the zebrafish larvae at embryo toxicity and transcriptional levels, providing some evidences for the toxic effects of triazole fungicides on non-target organisms.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146407DOI Listing
July 2021

Prediction of repeated-dose intravenous ketamine response in major depressive disorder using the GWAS-based machine learning approach.

J Psychiatr Res 2021 06 12;138:284-290. Epub 2021 Apr 12.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address:

Major depressive disorder (MDD) is one of the most common psychiatric disorders. Various clinical studies have shown that the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapid, robust, and sustained antidepressant effects. However, given the concerns about the adverse effects of ketamine on patients, it would be important to identify a set of biomarkers that could be used to predict clinical outcomes for its treatment. A total of 83 MDD patients received treatment with six ketamine infusions for up to 2 weeks and were classified into "responders" or "non-responders" based on an average change in the HAMD score >50% from baseline. A nested cross-validation approach was applied to prevent information leakage and overestimation of model performance. The initial dataset was divided randomly into training and test sets in a nested six-fold cross-validation. We first performed genome-wide logistic regression to find potentially significant variants related to treatment response and then selected the top SNPs based on the genetic association results using the random forests algorithm. Subsequently, six machine learning models were employed to construct prediction models by using ten-fold cross-validation. A series of model comparisons showed that the best performing fold was characterized by accuracy of 0.85, precision of 0.75, and a sensitivity of 1.00 with the support vector machine algorithm. Together, these findings demonstrated that the machine learning approach can predict the treatment outcomes of multiple ketamine infusions on the basis of the genotyping information of each participant.
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http://dx.doi.org/10.1016/j.jpsychires.2021.04.014DOI Listing
June 2021

Effects of polyethylene microplastics on the microbiome and metabolism in larval zebrafish.

Environ Pollut 2021 Aug 31;282:117039. Epub 2021 Mar 31.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, China. Electronic address:

Various microplastics (MPs) are found in the environment and organisms. MP residues in organisms can affect health; however, their impacts on metabolism in aquatic organisms remain unclear. In this study, zebrafish embryos were exposed to polyethylene MPs with sizes ranging from 1 to 4 μm at concentrations of 0, 10, 100, and 1000 μg/L for 7 days. Through qPCR technology, the results indicated that zebrafish exposed to polyethylene MPs exhibited significant change in microbes of the phyla Firmicutes, Bacteroidetes, Proteobacteria, and Verrucomicrobia, etc. Moreover, 16S RNA gene sequencing revealed that there was a significant difference in alpha diversity between the control and 1000 μg/L MP-treated groups. At the genus level, the abundance of Aeromonas, Shewanella, Microbacterium, Nevskia and Methyloversatilis have increased remarkably. Conversely, the abundance of Pseudomonas, Ralstonia and Stenotrophomonas were significant reduction after MPs exposure. In addition, the levels of TG (triglyceride), TCHO (total cholesterol), NEFA (nonesterified fatty acid), TBA (total bile acid), GLU (glucose) and pyruvic acid significantly changed in MP-treated larval zebrafish, indicating that their metabolism was disturbed by MPs. Transcriptional levels of glucose and lipid metabolism-related genes showed a decreasing trend. Furthermore, LC/MS-based nontargeted metabolomics analysis demonstrated that a total of 59 phospholipid-related substances exhibited significant changes in larval fish treated with 1000 μg/L MPs. The mRNA levels of phospholipid metabolism-related genes were also obviously changed. Pearson correlation analysis indicated that the abundance of Aeromonas, Shewanella and Chitinibacter bacteria showed a negative correlation with most phospholipids, while Nevskia, Parvibacter and Lysobacter showed a positive correlation with most phospholipids. Based on these results, it is suggested that 1-4 μm PE-MPs could impact the microbiome and metabolism of larval zebrafish. All of these results indicated that the health risk of MPs cannot be ignored.
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http://dx.doi.org/10.1016/j.envpol.2021.117039DOI Listing
August 2021

Health risks of chlorothalonil, carbendazim, prochloraz, their binary and ternary mixtures on embryonic and larval zebrafish based on metabolomics analysis.

J Hazard Mater 2021 02 10;404(Pt B):124240. Epub 2020 Oct 10.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Chlorothalonil (CTL), carbendazim (CBZ), and prochloraz (PCZ) are fungicides widely used in many countries. The use of these fungicides raises concerns because they are often applied together or used in the same agricultural area. However, the toxicity of these fungicides or mixtures, especially to aquatic organisms, has received limited attention. Here, embryonic and larval zebrafish were exposed to indicated concentrations of CTL, CBZ, and PCZ and their binary (CTL+CBZ, CTL+PCZ and CBZ+PCZ) and ternary (CTL+CBZ+PCZ) mixtures for 24 h. Based on metabolomics analysis, we observed that hundreds of metabolites were altered, and glycolysis metabolism and amino acid metabolism were the two most affected pathways. Interestingly, a total of 9 and 26 metabolites changed significantly in embryos and larvae treated with all fungicides, respectively. Among these altered metabolites, 2-aminoadipic acid (2-AAA) levels increased significantly in all groups, indicating that 2-AAA potentially represents a useful biomarker for evaluating the toxicity of fungicides. Furthermore, the joint effects of CTL+PCZ on embryos and larvae, especially on amino acid metabolism, were weaker than those in other groups, but combined treatment did not influence individual fungicidal activity. Data acquired from metabolomics provided important insight for understanding the mechanism by which fungicides or their mixtures affect zebrafish.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124240DOI Listing
February 2021

Clostridiales are predominant microbes that mediate psychiatric disorders.

J Psychiatr Res 2020 11 1;130:48-56. Epub 2020 Aug 1.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Research Center for Air Pollution and Health, Zhejiang University, China. Electronic address:

Background: An increasing number of studies have documented associations between psychiatric diseases and the gut microbiome. By taking genetic correlation and comorbidity of different psychiatric diseases into consideration, we hypothesized that different psychiatric diseases might share some similar microbial shift patterns. However, a deep understanding of whether and how those psychiatric disease-associated microbial dysbiosis spectrums are correlated is currently lacking.

Methods: In this study, we analyzed six case-control 16S amplicon sequencing datasets for psychiatric disorders, which included a total of 430 subjects, and compared microbial dysbiosis patterns across these studies.

Results: Different psychiatric diseases exhibited similar overall shift patterns. Significant correlations of overall shift patterns existed between schizophrenia and anorexia (p = 0.0008), as well as between schizophrenia and autism (p = 0.028). We identified 6 genera within order Clostridiales (genus Gemmiger, Faecalibacterium, Roseburia, Lachnospira, Anaerostipes, and two unclassified genera from family Lachnopsiraceae and Christensenellaceae) that were significantly depleted in multiple psychiatric diseases. Our further functional analysis revealed that depletion of these Clostridiales was associated with dysfunction in amino acid metabolism and carbohydrate metabolism. Short chain fatty acid (SCFA) producing bacteria Roseburia was the most important contributor for major KEGG (Kyoto Encyclopedia of Genes and Genomes) orthology entries involved in amino acid metabolism.

Conclusions: Our study revealed common microbial shift patterns across psychiatric disorders and found predominant psychiatry-associated intestinal microbes and functions. Depletion of Clostridiales (e.g., Roseburia) probably mediated different psychiatric diseases by dysfunction of intestinal amino acid metabolism and SCFA production. Furthermore, our study indicated that correlations of microbial shift patterns between psychiatric diseases may derived from their genetic associations. Such shared microbial dysbiosis patterns are intriguing for discovering biomarkers and investigating therapeutic targets for treating psychiatric diseases.
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http://dx.doi.org/10.1016/j.jpsychires.2020.07.018DOI Listing
November 2020

Sub-chronic carbendazim exposure induces hepatic glycolipid metabolism disorder accompanied by gut microbiota dysbiosis in adult zebrafish (Daino rerio).

Sci Total Environ 2020 Oct 9;739:140081. Epub 2020 Jun 9.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Carbendazim (CBZ) as a broad spectrum fungicide is widely used in the whole world to contorl plant diseases. With the application of CBZ in the agriculture, it has been detected in vegetables and fruits. Nowadays, it even has been detected in the watercourse and indoor dust. However, the toxic effects of CBZ on aquatic organisms have received limited attention. In this study, male adult zebrafish were exposed at 0, 30 and 100 μg/L CBZ for 21 days to assess its effects on hepatic glycolipid metabolism. After exposure, the body weight and length decreased, but the condition factor increased significantly. Some hepatic biochemical parameters including the levels of glucose, pyruvate, low density lipoprotein (LDL) and triglyceride (TG) decreased significantly in the liver of zebrafish after exposure with CBZ. Two transaminases alanine transaminase (ALT) and aspartate transaminase (AST) also increased significantly, indicating that subchronic CBZ exposure influenced the liver function. Moreover, the relative mRNA levels of some key genes related to the glycolysis and lipid metabolism in the liver also changed significantly. Furthermore, the transcriptome analysis showed that the carbon metabolism, lipid metabolism and detoxification metabolism were also affected in the liver of CBZ exposed zebrafish. Interestingly, we also found the amounts of the Firmicutes, Bacteroidetes, Actinobacteria, α-Proteobacteria, γ-Proteobacteria and Verrucomicrobia at phylum level significantly decreased in the gut. Sequencing V3-V4 region of 16S rRNA also demonstrated gut microbiota composition changed significantly according to weighted UniFrac distance analysis. Consequently, subchronic CBZ exposure induced hepatic metabolic disorder accompanied by gut microbiota dysbiosis in adult male zebrafish.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140081DOI Listing
October 2020

Negatively Charged Nanosheets Significantly Enhance the Energy-Storage Capability of Polymer-Based Nanocomposites.

Adv Mater 2020 Jun 13;32(25):e1907227. Epub 2020 May 13.

Hefei National Laboratory for Physical Sciences at the Microscale, Department of Physics and CAS Key Laboratory of Strongly-Coupled Quantum Matter Physics, University of Science and Technology of China, Hefei, 230026, P. R. China.

Polymer-based dielectric materials play a key role in advanced electronic devices and electric power systems. Although extensive research has been devoted to improve their energy-storage performances, it is a great challenge to increase the breakdown strength of polymer nanocomposites in terms of achieving high energy density and good reliability under high voltages. Here, a general strategy is proposed to significantly improve their breakdown strength and energy storage by adding negatively charged Ca Nb O nanosheets. A dramatically enhanced breakdown strength (792 MV m ) and the highest energy density (36.2 J cm ) among all flexible polymer-based dielectrics are observed in poly(vinylidene fluoride)-based nanocomposite capacitors. The strategy generalizability is verified by the similar substantial enhancements of breakdown strength and energy density in polystyrene-based nanocomposites. Phase-field simulations demonstrate that the further enhanced breakdown strength is ascribed to the local electric field, produced by the negatively charged Ca Nb O nanosheets sandwiched with the positively charged polyethyleneimine, which suppresses the secondary impact-ionized electrons and blocks the breakdown path in nanocomposites. The results demonstrate a new horizon of high-energy-density flexible capacitors.
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http://dx.doi.org/10.1002/adma.201907227DOI Listing
June 2020

Updated review of research on the gut microbiota and their relation to depression in animals and human beings.

Mol Psychiatry 2020 11 24;25(11):2759-2772. Epub 2020 Apr 24.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China.

The gut microbiota are being called the human "second brain," as they play a key role in the regulation of the central nervous system (CNS). Recent findings provide strong evidence for the presence of bidirectional communication networks between the gut microbiota and the CNS, and such crosstalk has been correlated with alterations in major depressive disorder (MDD) and other psychiatric disorders. Further, germ-free animal models have been used to investigate the effect of the microbiota on MDD and other psychiatric disorders, which have greatly expanded our knowledge of the role of the microbiota in the etiology of MDD and promoted causality studies of this psychiatric disorder and others as well. In this review, we first introduce the methodological approaches used for microbiota research and then provide an overview of current research progress on the modulatory function and composition of the gut microbiota in MDD and the therapeutic effect of probiotics that has been gained using data from human studies as well as animal experiments. Future research should focus on identification and characterization of specific bacterial strains involved in MDD with the hope of applying these findings in the prevention and treatment of MDD.
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http://dx.doi.org/10.1038/s41380-020-0729-1DOI Listing
November 2020

Polystyrene microplastic exposure disturbs hepatic glycolipid metabolism at the physiological, biochemical, and transcriptomic levels in adult zebrafish.

Sci Total Environ 2020 Mar 27;710:136279. Epub 2019 Dec 27.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Microplastics (MPs), which are new types of environmental pollutants, have recently received widespread attention worldwide. MPs can accumulate in the bodies of animals and in plants, and they can also enter the human body through the food chain. However, knowledge of the effects of MPs on the health of animals is still limited. In this experiment, adult male zebrafish were exposed to 20 or 100 μg/L of 5 μm polystyrene MP for 21 days in an attempt to determine the hepatic effects related to glycolipid metabolism at the biochemical and transcriptomic levels. It was found that body weight and condition factor decreased significantly in zebrafish after exposure to 20 and 100 μg/L polystyrene MP for 21 days. The transcription levels of major genes related to glycolipid metabolism decreased significantly in the liver. Correspondingly, the levels of major biochemical parameters, including Glu, pyruvic acid, α-ketoglutaric acid and IDH, were also decreased in the livers of exposed zebrafish, especially those in the 100 μg/L polystyrene MP-treated group. Moreover, the data on the hepatic transcriptome also confirmed that some genes related to fatty acid metabolism, amino acid metabolism and carbon metabolism tended to be decreased in the livers of exposed zebrafish. Taken together, our data confirmed that polystyrene PS-MP can induce hepatic glycolipid metabolism disorder at the physiological, biochemical, and transcriptomic levels in adult zebrafish after 21 days of exposure.
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http://dx.doi.org/10.1016/j.scitotenv.2019.136279DOI Listing
March 2020

Nuclear factor erythroid 2-related factor 2 activation mediates hyperhomocysteinemia-associated lipolysis suppression in adipocytes.

Exp Biol Med (Maywood) 2018 07;243(11):926-933

1 College of Medical Laboratory Science and Technology, Harbin Medical University (Daqing), Daqing 163319, Heilongjiang, P. R. China.

Hyperhomocysteinemia (HHcy) is associated with suppressed lipolytic response in adipocytes/adipose tissue, however, the underlying mechanism remains to be extensively studied. Nuclear factor erythroid 2-related factor 2 (Nrf2), a master transcriptional factor regulating antioxidant generation, has been recently reported to mediate lipid metabolism. Employing both fully differentiated 3T3-L1 adipocytes and male C57BL/6 mice, in the present study, we investigated the potential involvement of Nrf2 activation in HHcy-mediated lipolytic suppression. Our results showed that homocysteine (Hcy) treatment resulted in suppressed lipolysis, evidenced by increased intracellular triglyceride (TG) accumulation, decreased glycerol and free fatty acid (FFA) in fully differentiated 3T3-L1 adipocytes. Interestingly, Hcy exposure was associated with Nrf2 activation in adipocytes. Further studies showed that Nrf2 knockdown via siRNA transfection ameliorated Hcy-induced glycerol release in adipocytes. On the contrary, Nrf2 activators, epigallocatechin gallate (EGCG) and tert-butylhydroquinone (t-BHQ), increased intracellular TG content and decreased glycerol release in adipocytes. Importantly, our in vitro observations were corroborated by our in vivo findings, in which Hcy feeding (0.1% wt/vol) for four weeks induced Nrf2 expression in adipose tissue and lowered circulating FFA and glycerol levels in mice. Furthermore, EGCG injection (5 mg/kg/d) decreased circulating glycerol levels in comparison to the control group in mice. In conclusion, these results indicated that Nrf2 activation in response to HHcy plays an important role in mediating Hcy-suppressed lipolysis in adipocytes.
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http://dx.doi.org/10.1177/1535370218788520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108053PMC
July 2018

Clinical and economic impact of pharmacist interventions on sampled outpatient prescriptions in a Chinese teaching hospital.

BMC Health Serv Res 2018 07 4;18(1):519. Epub 2018 Jul 4.

Department of Pharmacy, First Affiliated Hospital of Nanjing Medical University, No 300 Guangzhou Road, Nanjing City, Jiangsu Province, 210029, People's Republic of China.

Background: Limited studies have evaluated the effectiveness of pharmacist interventions on outpatient prescription. The goal of this study was to evaluate the clinical and economic impacts of pharmacist interventions on randomly sampled outpatient prescriptions.

Method: Outpatient prescriptions of our hospital were sampled automatically and reviewed by pharmacists since 2011. Pharmacists intervened in inappropriate prescriptions (IPs) real-timely, and summarized and analyzed the information monthly. Cost-benefit analysis was performed to estimate the economic benefit of the pharmacist intervention.

Results: From 2011 to 2016, pharmacists reviewed 101,271 prescriptions and intervened in 5155 prescriptions. With the interventions of pharmacists, the number of IPs decreased from 1845 to 238, while the inappropriate percentage decreased from 12.60 to 1.22%. The inappropriate rates of different departments and the types decreased annually. IPs were mainly from the Department of Medicine and Department of Surgery and category 1 (Non-indicated medications) in all years. The benefit-to-cost ratios of pharmacist interventions were always more than 1. In the same years, the benefit-to-cost ratios in public payments were higher than those with insurance and self-payment.

Conclusion: This form of pharmacist intervention constitutes a method that showed positive clinical and economic benefits and is worth expanding in large hospitals. Pharmacists should pay more attention on prescriptions in department of surgery or prescriptions with public payments.
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http://dx.doi.org/10.1186/s12913-018-3306-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031100PMC
July 2018

Poly(ADP-Ribose) Polymerase Inhibitor PJ34 Attenuated Hepatic Triglyceride Accumulation in Alcoholic Fatty Liver Disease in Mice.

J Pharmacol Exp Ther 2018 03 9;364(3):452-461. Epub 2018 Jan 9.

College of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, Heilongjiang, China (S.H., B.Z., Y.C., Y.L., X.L., Z.B., Z.W.); Fuxin Center Hospital, Fuxin, Jilin, China (H.L.); and Department of Kinesiology and Nutrition, University of Illinois, Chicago, Illinois (Z.S.)

Poly(ADP-ribose) polymerase (PARP) is an NAD-consuming enzyme and its specific role in the pathogenesis of alcoholic fatty liver disease (AFLD) remains elusive. In this study, we applied PJ34 [-(5,6-dihydro-6-oxo-2-phenanthridinyl)-2-acetamide hydrochloride] to inhibit hepatic PARP activity to examine the corresponding pathologic alteration in AFLD in mice and the underlying molecular mechanism. We found that PJ34 decreased the intracellular triglyceride (TG) content in hepatocytes. Moreover, PJ34 suppressed the gene expression of diglyceride acyltransferases DGAT1 and DGAT2 and elevated intracellular NAD levels in hepatocytes. These mechanistic observations were validated in alcohol-fed mice injected with PJ34 intraperitoneally. Our results indicate that the PJ34 injection attenuated hepatic TG accumulation in alcohol-fed mice. Furthermore, PJ34 injection lowered the gene expression of hepatic sterol regulatory element binding protein 1c, DGAT1, and DGAT2, whereas PJ34 injection augmented hepatic NAD levels in alcohol-fed mice. Finally, nicotinamide riboside supplementation alleviated hepatic TG accumulation in alcohol-fed mice. These data indicate that applying PARP-specific inhibitor PJ34 by intraperitoneal injection attenuated hepatic NAD depletion and TG accumulation in alcohol-fed mice and may be a potential candidate for use in AFLD therapy.
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http://dx.doi.org/10.1124/jpet.117.243105DOI Listing
March 2018

Rational Design of α-Fe2O3/Reduced Graphene Oxide Composites: Rapid Detection and Effective Removal of Organic Pollutants.

ACS Appl Mater Interfaces 2016 Mar 2;8(10):6431-8. Epub 2016 Mar 2.

Department of Polymer Science and Engineering, University of Science and Technology of China , Hefei 230026, China.

α-Fe2O3/reduced graphene oxide (α-Fe2O3/rGO) composites are rationally designed and prepared to integrate organic pollutants detection and their photocatalytic degradation. Specifically, the composites are used as the substrate for surface-enhanced Raman scattering (SERS) to detect rhodamine 6G (R6G). Repeatable strong SERS signals could be obtained with R6G concentration as low as 10(-5) M. In addition, the substrate exhibits self-cleaning properties under solar irradiation. Compared with pure α-Fe2O3 and α-Fe2O3/rGO mechanical mixtures, the α-Fe2O3/rGO composites show much higher photocatalytic activity and much greater Raman enhancement factor. After 10 cycling measurements, the photodegradation rate of R6G could be maintained at 90.5%, indicating high stability of the photocatalyst. This study suggests that the α-Fe2O3/rGO composites would serve both as recyclable SERS substrate and as excellent visible light photocatalyst.
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http://dx.doi.org/10.1021/acsami.5b11292DOI Listing
March 2016

Ventricular tachyarrhythmias in rats with acute myocardial infarction involves activation of small-conductance Ca2+-activated K+ channels.

Am J Physiol Heart Circ Physiol 2013 Jan 19;304(1):H118-30. Epub 2012 Oct 19.

Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People's Republic of China.

In vitro experiments have shown that the upregulation of small-conductance Ca(2+)-activated K(+) (SK) channels in ventricular epicardial myocytes is responsible for spontaneous ventricular fibrillation (VF) in failing ventricles. However, the role of SK channels in regulating VF has not yet been described in in vivo acute myocardial infarction (AMI) animals. The present study determined the role of SK channels in regulating spontaneous sustained ventricular tachycardia (SVT) and VF, the inducibility of ventricular tachyarrhythmias, and the effect of inhibition of SK channels on spontaneous SVT/VF and electrical ventricular instability in AMI rats. AMI was induced by ligation of the left anterior descending coronary artery in anesthetized rats. Spontaneous SVT/VF was analyzed, and programmed electrical stimulation was performed to evaluate the inducibility of ventricular tachyarrhythmias, ventricular effective refractory period (VERP), and VF threshold (VFT). In AMI, the duration and episodes of spontaneous SVT/VF were increased, and the inducibility of ventricular tachyarrhythmias was elevated. Pretreatment in the AMI group with the SK channel blocker apamin or UCL-1684 significantly reduced SVT/VF and inducibility of ventricular tachyarrhythmias (P < 0.05). Various doses of apamin (7.5, 22.5, 37.5, and 75.0 μg/kg iv) inhibited SVT/VF and the inducibility of ventricular tachyarrhythmias in a dose-dependent manner. Notably, no effects were observed in sham-operated controls. Additionally, VERP was shortened in AMI animals. Pretreatment in AMI animals with the SK channel blocker significantly prolonged VERP (P < 0.05). No effects were observed in sham-operated controls. Furthermore, VFT was reduced in AMI animals, and block of SK channels increased VFT in AMI animals, but, again, this was without effect in sham-operated controls. Finally, the monophasic action potential duration at 90% repolarization (MAPD(90)) was examined in the myocardial infarcted (MI) and nonmyocardial infarcted areas (NMI) of the left ventricular epicardium. Electrophysiology recordings showed that MAPD(90) in the MI area was shortened in AMI animals, and pretreatment with SK channel blocker apamin or UCL-1684 significantly prolonged MAPD(90) (P < 0.05) in the MI area but was without effect in the NMI area or in sham-operated controls. We conclude that the activation of SK channels may underlie the mechanisms of spontaneous SVT/VF and susceptibility to ventricular tachyarrhythmias in AMI. Inhibition of SK channels normalized the shortening of MAPD(90) in the MI area, which may contribute to the inhibitory effect on spontaneous SVT/VF and inducibility of ventricular tachyarrhythmias in AMI.
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http://dx.doi.org/10.1152/ajpheart.00820.2011DOI Listing
January 2013
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