Publications by authors named "Yimin Mao"

62 Publications

Association between intake of sweetened beverages with all-cause and cause-specific mortality: a systematic review and meta-analysis.

J Public Health (Oxf) 2021 Apr 9. Epub 2021 Apr 9.

General Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University; Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis; Henan Engineering Research Center for Critical Care Medicine, Zhengzhou 450052, China.

Background: Conclusions remain controversial between the consumption of sugar and artificially sweetened beverages (SSBs and ASBs) and mortality.

Methods: We systematically searched the PubMed, Embase, Cochrane Library and Web of Science databases from their inception date to 1st January 2020, prospective cohort studies researching the mortality risk and SSBs or ASBs consumption were included. Random effects meta-analyses and dose-response analyses were performed to measure the association. Subgroup analyses and sensitivity analyses were further performed to explore the source of heterogeneity. Publication bias was assessed by Funnel plots and Egger's regression test.

Results: Across all 15 cohorts, 1211 470 participants were included. High SSB consumption was associated with a higher risk of all-cause mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.06-1.19, P < 0.001; and cardiovascular disease [CVD] mortality [HR 1.20, 95% CI, 1.05-1.38, P < 0.001]), and high ASBs consumption showed similar result (HR 1.12, 95% CI, 1.04-1.21, P = 0.001 for all-cause mortality and HR 1.23, 95% CI, 1.00-1.50, P = 0.049 for CVD mortality), both showed a linear dose-response relationship.

Conclusions: High consumption of both ASBs and SSBs showed significant associations with a higher risk of CVD mortality and all-cause mortality. This information may provide ideas for decreasing the global burden of diseases by reducing sweetened beverage intake.
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http://dx.doi.org/10.1093/pubmed/fdab069DOI Listing
April 2021

Drug-induced liver injury: Asia Pacific Association of Study of Liver consensus guidelines.

Hepatol Int 2021 Feb 27. Epub 2021 Feb 27.

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.

Idiosyncratic drug-induced liver injury mimics acute and chronic liver disease. It is under recognized and underrecognised because of the lack of pathognomonic diagnostic serological markers. Its consequences may vary from being asymptomatic to self-limiting illness to severe liver injury leading to acute liver failure. Its incidence is likely to be more common in Asia than other parts of the world, mainly because of hepatotoxicity resulting from the treatment of tuberculosis disease and the ubiquitous use of traditional and complimentary medicines in Asian countries. This APASL consensus guidelines on DILI is a concise account of the various aspects including current evidence-based information on DILI with special emphasis on DILI due to antituberculosis agents and traditional and complementary medicine use in Asia.
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http://dx.doi.org/10.1007/s12072-021-10144-3DOI Listing
February 2021

A modified Khorana score as a risk assessment tool for predicting venous thromboembolism in newly diagnosed advanced lung cancer.

J Thromb Thrombolysis 2021 Feb 18. Epub 2021 Feb 18.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, Henan, China.

The aim of this study was to evaluate the Khorana score and modified Khorana score as risk assessment tools for predicting the development of VTE in newly diagnosed advanced lung cancer. Information on the clinical data and laboratory indicators of the study group between 2014 and 2018 and the validation group between January 2019 to June 2020 of newly diagnosed advanced lung cancer patients at The First Affiliated Hospital of Henan University of Science and Technology was collected. We conducted an analysis of the risk factors affecting VTE development and the predictive risk value of the Khorana score and the modified Khorana score for VTE in newly diagnosed advanced lung cancer patients. A total of 124 patients were included in the study group. D-dimer is an independent risk factor for VTE in newly diagnosed advanced lung cancer patients (OR 1.620, 95% CI 1.220, 2.152, p = 0.001). The best cutoff value of D -dimer for the prediction of VTE development risk was 1.14 mg/L. The AUC of the Khorana score to predict the occurrence risk of VTE in newly diagnosed advanced lung cancer patients was 0.706; when the best cutoff value was 2, the sensitivity was 70.83%, and the specificity was 65%. The AUC of the modified Khorana score was 0.870; when the cutoff value was 2, the sensitivity was 100%, and the specificity was 50%. A total of 237 patients were included in the validation group, the AUC of the modified Khorana score for predicting the occurrence risk of VTE was 0.875; when the cutoff value was 2, the sensitivity was 100%, and the specificity was 52.1%. The modified Khorana score after incorporating D-dimer has a higher predictive value for the occurrence risk of VTE in newly diagnosed lung cancer patients; when the score ≥ 2, its sensitivity is higher, and it can more fully identify high-risk groups of VTE.
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http://dx.doi.org/10.1007/s11239-021-02396-5DOI Listing
February 2021

Ultra-small angle neutron scattering to study droplet formation in polyelectrolyte complex coacervates.

Methods Enzymol 2021 25;646:261-276. Epub 2020 Jul 25.

Materials Science and Engineering Division, Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD, United States.

Associating soft matter such as surfactants, polymers, proteins, and liposomes, may form structures with dimensions not readily accessible by optical methods. Scattering methods can provide detailed information about the mechanism of associative phase separation including nucleation density, size, and shape. Ultra-small angle neutron scattering, a reciprocal space method, provides sensitivity to submicron to micron-scale structures in a non-invasive manner and described in the context of nucleation and growth of dilute droplets formed by a temperature jump into the meta-stable region of polyelectrolyte complex coacervates.
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http://dx.doi.org/10.1016/bs.mie.2020.07.001DOI Listing
July 2020

Aggregation Controlled Charge Generation in Fullerene Based Bulk Heterojunction Polymer Solar Cells: Effect of Additive.

Polymers (Basel) 2020 Dec 30;13(1). Epub 2020 Dec 30.

Department of Chemistry, Physics and Materials Science, Fayetteville State University, Fayetteville, NC 28301, USA.

Optimization of charge generation in polymer blends is crucial for the fabrication of highly efficient polymer solar cells. While the impacts of the polymer chemical structure, energy alignment, and interface on charge generation have been well studied, not much is known about the impact of polymer aggregation on charge generation. Here, we studied the impact of aggregation on charge generation using transient absorption spectroscopy, neutron scattering, and atomic force microscopy. Our measurements indicate that the 1,8-diiodooctane additive can change the aggregation behavior of poly(benzodithiophene-alt-dithienyl difluorobenzotriazole (PBnDT-FTAZ) and phenyl-C61-butyric acid methyl ester (PCBM)polymer blends and impact the charge generation process. Our observations show that the charge generation can be optimized by tuning the aggregation in polymer blends, which can be beneficial for the design of highly efficient fullerene-based organic photovoltaic devices.
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http://dx.doi.org/10.3390/polym13010115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795443PMC
December 2020

Tolvaptan therapy of Chinese cirrhotic patients with ascites after insufficient diuretic routine medication responses: a phase III clinical trial.

BMC Gastroenterol 2020 Nov 19;20(1):391. Epub 2020 Nov 19.

School of Medicine Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, No. 145, Middle Shandong Road, Shanghai, 200001, China.

Background: To determine the safety and efficacy of different doses of tolvaptan for treating Chinese cirrhotic patients with or without hyponatraemia who still had ascites after routine therapy with diuretics.

Methods: In the present placebo-controlled, randomized, double-blinded, multicentre clinical trial, patients with cirrhotic ascites who failed to adequately respond to a combination of an aldosterone antagonist plus an orally administered loop diuretic were randomly placed at a 4:2:1 ratio into 3 groups [the 15 mg/day tolvaptan group (N = 301), 7.5 mg/day tolvaptan group (N = 153) and placebo group (N = 76)] for 7 days of treatment. The effects and safety were evaluated on days 4 and 7. A change in body weight from baseline on day 7 of treatment was the primary endpoint.

Results: The administration of 7.5 or 15 mg/day tolvaptan significantly decreased body weight from baseline on day 7 of treatment compared to that with placebo treatment (P = 0.026; P = 0.001). For the secondary endpoints, changes in abdominal circumference from baseline and improvements in ascites were markedly different in the treatment groups and the placebo group on day 7 (P = 0.05, P = 0.002 and P = 0.037, P = 0.003), but there was no difference between the 7.5 mg/day and 15 mg/day dosage groups. The 24-h cumulative urine volume was higher in the 7.5 mg/day and 15 mg/day tolvaptan groups than the placebo group (P = 0.002, P < 0.001) and was greater in the 15 mg/day tolvaptan group than the 7.5 mg/day tolvaptan group (P = 0.004). Sodium serum concentrations were higher in patients with hyponatraemia after tolvaptan treatment, with no significant difference between the two dosage groups. The incidence of serious adverse drug reactions was not different between the groups (P = 0.543).

Conclusions: Tolvaptan treatment at 7.5 mg per day might be a good therapeutic choice for Chinese cirrhotic patients with ascites who did not achieve satisfactory clinical responses to previous treatment regimens with combination therapy with an aldosterone antagonist and an orally administered loop diuretic.

Trial Registration: NCT01349348. Retrospectively registered May 2011.
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http://dx.doi.org/10.1186/s12876-020-01536-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678173PMC
November 2020

Corrigendum to "Efficacy and safety of Sildenafil treatment in pulmonary hypertension caused by chronic obstructive pulmonary disease: A meta-analysis" [Life Sci. 257 (15) (September 2020) 118001].

Life Sci 2020 Oct 22;259:118471. Epub 2020 Sep 22.

Department of Respiratory Medicine, Respiratory Diseases Institute, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China. Electronic address:

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http://dx.doi.org/10.1016/j.lfs.2020.118471DOI Listing
October 2020

Efficacy and safety of Sildenafil treatment in pulmonary hypertension caused by chronic obstructive pulmonary disease: A meta-analysis.

Life Sci 2020 Sep 4;257:118001. Epub 2020 Jul 4.

Department of Respiratory Medicine, Respiratory Diseases Institute, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China. Electronic address:

Aims: Pulmonary hypertension (PH) is a severe and prevalent complication of chronic obstructive pulmonary disease (COPD), with low quality of life and poor prognosis. This study was designed to evaluate the efficacy and safety of Sildenafil in the treatment of PH caused by COPD (COPD-PH) and provide reference for clinical treatment.

Materials And Methods: We systematically searched PubMed, EMBASE, Cochrane Library, Clinical Trials.gov databases, Wanfang Data and CNKI for comprehensive literature reporting Sildenafil for randomized controlled trials (RCT) of COPD-PH. Quality assessment, data analysis used the modified Jadad scale and RevMan5.3 software.

Key Findings: A total of 9 RCTs involving 579 patients were included in our study. The primary outcome measure was Six minutes walking distance (6MWD). Secondary observations were Pulmonary artery systolic pressure (PASP), Borg dyspnea index, and Survey scale (SF-36). Our data demonstrate that Sildenafil can improve 6WMD [29.64, 95% CI (13.78, 45.50), P < 0.00001] and PASP [-7.86, 95% CI (-11.26, -4.46) P < 0.00001] of COPD-PH, compared with the control group. However, SF-36 [2.64, 95% CI (-6.85, 12.14) P = 0.59] and Borg dyspnea index [-0.28, 95% CI (-1.08, 0.52) P = 0.49] have no significant difference between those two groups. Adverse reactions in the Sildenafil treatment group were tolerated headaches and digestive symptoms, which were relatively safe.

Significance: Available clinical evidence indicates that Sildenafil seems to be safe and effective for COPD-PH and can improve the patients' 6WMD. However, large-sample, high-quality multicenter RCTs are still needed to provide stronger evidence-based medical evidence.
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http://dx.doi.org/10.1016/j.lfs.2020.118001DOI Listing
September 2020

Rational and design of the China Pulmonary Thromboembolism Registry Study (CURES): A prospective multicenter registry.

Int J Cardiol 2020 10 6;316:242-248. Epub 2020 Jun 6.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, PR China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, PR China; National Clinical Research Center for Respiratory Disease, Beijing, PR China; Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, PR China; Department of Respiratory Medicine, Capital Medical University, Beijing, PR China. Electronic address:

Background: Epidemiological data on pulmonary embolism (PE) in China needs to be updated and reported. The China Pulmonary Thromboembolism Registry Study (CURES) is designed to provide the cross-sectional spectrum and chronological trends of PE in China, as well as to reveal the intrinsic etiology and pathogenesis of the disease.

Methods And Design: The CURES is an ongoing large prospective multicenter registry, which was originally initiated in January 2009 via enrolling suspected or confirmed PE or PE with DVT (deep venous thrombosis) patients and assessed their in-hospital outcomes. As of July 2011, in order to determine the PE-relevant short-term outcomes, enrolled participants were followed-up for at least three months in a longitudinal manner. Since August 2016, with the launch and development of precision medicine research scheme in China, the main principle investigators of CURES decided to collect enrolled patients' blood samples with regular follow-ups every three or six months for at least two years (for long-term outcomes). Up to 31 December 2019, the CURES has enrolled 14,937 eligible patients and collected 1500 blood samples of patients from 100 medical centers in the China PE-DVT network. The study protocol has been approved by the China-Japan Friendship Hospital ethics committee, and all collaborating centers received approvals from their local ethics committee. All patients provided written or verbal informed consent to their participation.

Conclusions: Findings of the CURES will be valuable for revealing the natural history of PE, and facilitating better disease management in China. Registration Number inClinicalTrials.gov:NCT02943343.
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http://dx.doi.org/10.1016/j.ijcard.2020.05.087DOI Listing
October 2020

Computationally aided, entropy-driven synthesis of highly efficient and durable multi-elemental alloy catalysts.

Sci Adv 2020 Mar 13;6(11):eaaz0510. Epub 2020 Mar 13.

Department of Materials Science and Engineering, University of Maryland, College Park, MD 20742, USA.

Multi-elemental alloy nanoparticles (MEA-NPs) hold great promise for catalyst discovery in a virtually unlimited compositional space. However, rational and controllable synthesize of these intrinsically complex structures remains a challenge. Here, we report the computationally aided, entropy-driven design and synthesis of highly efficient and durable catalyst MEA-NPs. The computational strategy includes prescreening of millions of compositions, prediction of alloy formation by density functional theory calculations, and examination of structural stability by a hybrid Monte Carlo and molecular dynamics method. Selected compositions can be efficiently and rapidly synthesized at high temperature (e.g., 1500 K, 0.5 s) with excellent thermal stability. We applied these MEA-NPs for catalytic NH decomposition and observed outstanding performance due to the synergistic effect of multi-elemental mixing, their small size, and the alloy phase. We anticipate that the computationally aided rational design and rapid synthesis of MEA-NPs are broadly applicable for various catalytic reactions and will accelerate material discovery.
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http://dx.doi.org/10.1126/sciadv.aaz0510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069714PMC
March 2020

High-throughput, combinatorial synthesis of multimetallic nanoclusters.

Proc Natl Acad Sci U S A 2020 03 10;117(12):6316-6322. Epub 2020 Mar 10.

Department of Materials Science and Engineering, University of Maryland, College Park, MD 20742;

Multimetallic nanoclusters (MMNCs) offer unique and tailorable surface chemistries that hold great potential for numerous catalytic applications. The efficient exploration of this vast chemical space necessitates an accelerated discovery pipeline that supersedes traditional "trial-and-error" experimentation while guaranteeing uniform microstructures despite compositional complexity. Herein, we report the high-throughput synthesis of an extensive series of ultrafine and homogeneous alloy MMNCs, achieved by 1) a flexible compositional design by formulation in the precursor solution phase and 2) the ultrafast synthesis of alloy MMNCs using thermal shock heating (i.e., ∼1,650 K, ∼500 ms). This approach is remarkably facile and easily accessible compared to conventional vapor-phase deposition, and the particle size and structural uniformity enable comparative studies across compositionally different MMNCs. Rapid electrochemical screening is demonstrated by using a scanning droplet cell, enabling us to discover two promising electrocatalysts, which we subsequently validated using a rotating disk setup. This demonstrated high-throughput material discovery pipeline presents a paradigm for facile and accelerated exploration of MMNCs for a broad range of applications.
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http://dx.doi.org/10.1073/pnas.1903721117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104385PMC
March 2020

Protein-protein interactions underlying the behavioral and psychological symptoms of dementia (BPSD) and Alzheimer's disease.

PLoS One 2020 17;15(1):e0226021. Epub 2020 Jan 17.

Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.

Alzheimer's Disease (AD) is a devastating neurodegenerative disorder currently affecting 45 million people worldwide, ranking as the 6th highest cause of death. Throughout the development and progression of AD, over 90% of patients display behavioral and psychological symptoms of dementia (BPSD), with some of these symptoms occurring before memory deficits and therefore serving as potential early predictors of AD-related cognitive decline. However, the biochemical links between AD and BPSD are not known. In this study, we explored the molecular interactions between AD and BPSD using protein-protein interaction (PPI) networks built from OMIM (Online Mendelian Inheritance in Man) genes that were related to AD and two distinct BPSD domains, the Affective Domain and the Hyperactivity, Impulsivity, Disinhibition, and Aggression (HIDA) Domain. Our results yielded 8 unique proteins for the Affective Domain (RHOA, GRB2, PIK3R1, HSPA4, HSP90AA1, GSK3beta, PRKCZ, and FYN), 5 unique proteins for the HIDA Domain (LRP1, EGFR, YWHAB, SUMO1, and EGR1), and 6 shared proteins between both BPSD domains (APP, UBC, ELAV1, YWHAZ, YWHAE, and SRC) and AD. These proteins might suggest specific targets and pathways that are involved in the pathogenesis of these BPSD domains in AD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226021PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968845PMC
April 2020

A network analysis revealed the essential and common downstream proteins related to inguinal hernia.

PLoS One 2020 7;15(1):e0226885. Epub 2020 Jan 7.

Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.

Although more than 1 in 4 men develop symptomatic inguinal hernia during their lifetime, the molecular mechanism behind inguinal hernia remains unknown. Here, we explored the protein-protein interaction network built on known inguinal hernia-causative genes to identify essential and common downstream proteins for inguinal hernia formation. We discovered that PIK3R1, PTPN11, TGFBR1, CDC42, SOS1, and KRAS were the most essential inguinal hernia-causative proteins and UBC, GRB2, CTNNB1, HSP90AA1, CBL, PLCG1, and CRK were listed as the most commonly-involved downstream proteins. In addition, the transmembrane receptor protein tyrosine kinase signaling pathway was the most frequently found inguinal hernia-related pathway. Our in silico approach was able to uncover a novel molecular mechanism underlying inguinal hernia formation by identifying inguinal hernia-related essential proteins and potential common downstream proteins of inguinal hernia-causative proteins.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226885PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946160PMC
April 2020

Configurational conditions of national carbon intensity: a fuzzy set analysis of 136 countries.

Authors:
Yimin Mao

Environ Sci Pollut Res Int 2019 Nov 14;26(31):32446-32459. Epub 2019 Oct 14.

School of Public Administration, Zhejiang Gongshang University, No. 18, Xuezheng Str., Xiasha University Town, Hangzhou, 310018, China.

Drawing on the insights from the literature in environmental economics and politics, this study examines the configurational conditions of national carbon intensity by constructing a new analytical framework integrating six factors, i.e. population, affluence, industrial structure, energy intensity, urbanization rate and democracy. A fuzzy set analysis of 136 countries shows that national carbon intensity is not determined by any single factor but rather by the combined effects of multiple factors. There are two configurational pathways to low-carbon development while four pathways to high-carbon development, each with its own configuration. Low-carbon development occurs most often in those affluent, highly urbanized and democratic countries with low intensity of energy use, while high-carbon development is most likely in those small, poor countries with high intensity of energy use. This study also shows that the role of particular factor should be understood in the context as its combinations with different sets of other factors may produce opposite effects on national carbon intensity. That is, the policy efforts concentrated on single factor may be ineffective to reduce carbon intensity. These findings permit a more contextualized and systematic understanding of the determinants of national carbon intensity.
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http://dx.doi.org/10.1007/s11356-019-06471-6DOI Listing
November 2019

Emergence and Characterization of a Novel IncP-6 Plasmid Harboring and Genes in Isolates.

Front Microbiol 2019 12;10:2132. Epub 2019 Sep 12.

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

The dissemination of carbapenemases (KPCs) among Gram-negative bacteria is an important threat to global health. However, KPC-producing bacteria from environmental samples are rarely reported. This study aimed to elucidate the underlying resistance mechanisms of three carbapenem-resistant isolates recovered from river sediment samples. Pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS) analysis indicated a close evolutionary relationship among isolates. S1-PFGE, Southern blot and conjugation assays confirmed the presence of and genes on a non-conjugative plasmid in these isolates. Plasmid analysis further showed that pKPC-1713 is an IncP-6 plasmid with a length of 53,205 bp, which can be transformed into DH5α strain and mediated carbapenems and quinolones resistance. The plasmid backbone of p1713-KPC demonstrated 99% sequence identity to that of IncP-6-type plasmid pKPC-cd17 from spp. and IncP-6-type plasmid: 1 from at 74% coverage. A 14,808 bp insertion sequence was observed between gene and hypothetical protein in p1713-KPC, which include the quinolone resistance gene. Emergence of plasmid-borned and genes from isolates highlights their possible dissemination into the environment. Therefore, potential detection of such plasmids from clinical isolates should be closely monitored.
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http://dx.doi.org/10.3389/fmicb.2019.02132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751286PMC
September 2019

Reply.

Gastroenterology 2019 11 9;157(5):1439-1440. Epub 2019 Sep 9.

Liver Disease Center of Naval 905 Hospital and, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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http://dx.doi.org/10.1053/j.gastro.2019.08.047DOI Listing
November 2019

Efficacy and safety of magnesium isoglycyrrhizinate injection in patients with acute drug-induced liver injury: A phase II trial.

Liver Int 2019 11 21;39(11):2102-2111. Epub 2019 Aug 21.

Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Drug-induced liver injury (DILI) is the most common reason for a drug to be withdrawn from the market. Apart from stopping the offending drug, no regimens are available for treating idiosyncratic DILI in clinical practice.

Methods: We carried out a randomized, double-blind, multidoses, active drug controlled, multicentre phase II trial to assess the safety and efficacy of the study drug, magnesium isoglycyrrhizinate (MgIG), as compared to tiopronin, a standard therapy for DILI in China. The primary outcome was the proportion of alanine aminotransferase (ALT) normalization at week 4 after study drug administration. Logistic regression was used to examine the odds of ALT normalization between low dose (Group A) and high dose (Group B) vs active control (Group C).

Results: One hundred and seventy-four eligible subjects were randomized and enrolled into three groups: 59 in group A, 56 in group B and 59 in group C. It was shown that group A and group B lowered ALT level even at early stage of study drug administration; when compared with Group C (61.02%), the proportions of ALT normalization at week 4 were significantly greater in Group A (84.75%, P = .0029) and Group B (85.71%, P = .0037) respectively. The results from the univariate logistic model showed that the odds of ALT normalized among subjects in Group A were about 3.6 times greater (OR = 3.55, 95% CI: 1.47-8.57, P = .0049) than subjects in Group C. Similar effect was observed among subjects in Group B (OR = 3.83, 95% CI: 1.54-9.55, P = .0039).

Conclusions: This trial provided preliminary evidence that MgIG is an effective and safe treatment for patients with acute DILI.
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http://dx.doi.org/10.1111/liv.14204DOI Listing
November 2019

Molecular partitioning in ternary solutions of cellulose.

Carbohydr Polym 2019 Sep 23;220:157-162. Epub 2019 May 23.

Department of Materials Science and Engineering, University of Maryland, College Park, MD, 20742, United States; Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD, 20899, United States. Electronic address:

Neutron scattering measurements on the structure and dynamics of ternary solutions of microcrystalline cellulose (MC) in mixtures of an ionic liquid (IL) 1-ethyl-3-methylimidazolium acetate and a polar organic solvent dimethylformamide (DMF) have shown that MC can be fully dissolved in solvent mixtures. Data also show the molecular partitioning of IL into coexisting states. The structure partitioning is manifested as IL adsorbed to cellulose molecules with additional IL self-assembled to form clusters in solution, while the dynamics partitioning shows dynamical heterogeneities of the IL with slow dynamics resembling neat IL and fast dynamics being coupled with the solvent. The composition dependence of the molecular partitioning results in a solubility gap in dilute cellulose solutions and a phase boundary criterion of the molar ratio of IL / MC ∼ 3 in more concentrated regimes. The two characteristics together define the main features of the dissolution phase diagram of ternary cellulose mixtures of MC / IL / DMF at the room temperature.
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http://dx.doi.org/10.1016/j.carbpol.2019.05.054DOI Listing
September 2019

Turnover of bile acids in liver, serum and caecal content by high-fat diet feeding affects hepatic steatosis in rats.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 10 4;1864(10):1293-1304. Epub 2019 Jun 4.

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Background: Bile acids (BAs) participate in lipid absorption and serve as metabolic regulatory factors in gut-liver communication. To date, there are no studies on the systemic patterns of BAs in the serum, liver, and gut in the same non-alcoholic fatty liver disease (NAFLD) model.

Methods: A targeted metabolomics approach and 16S rRNA sequencing were used to identify the profile of BAs and connection between BAs and microbiota. The role and mechanism of altered BAs on hepatic steatosis were investigated.

Findings: In the liver, the composition of taurocholic acid (TCA) was increased, but taurohyodeoxycholic acid (THDCA) and ursodeoxycholic acid (UDCA) were decreased. In the gut, the deconjugated form of TCA (cholic acid (CA)) was increased, while the deconjugated forms of THDCA (α-hyodeoxycholic acid (HDCA)) and ω-muricholic acid (ωMCA) were decreased. In the serum, the composition of TCA was increased, while both HDCA and THDCA were decreased. THDCA induced the gene expression of apolipoprotein, bile secretion-related proteins, and cytochrome P450 family but suppressed inflammatory response genes expression in steatotic hepatocytes by RNAseq analysis. THDCA ameliorated neutral lipid accumulation and improved insulin sensitivity in primary rat hepatocytes. The decreased HDCA level correlated with the level of Bacteroidetes, while the level of CA correlated with the levels of Firmicutes and Verrucomicrobia but correlated inversely with Bacteroidetes.

Conclusion: BAs profiles in the serum, liver and caecal content were altered in a rat NAFLD model, which may affect hepatic lipid accumulation and correlate with gut dysbiosis.
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http://dx.doi.org/10.1016/j.bbalip.2019.05.016DOI Listing
October 2019

Long-term efficacy and safety of tenofovir disoproxil fumarate in Chinese patients with chronic hepatitis B: 5-year results.

Hepatol Int 2019 May 11;13(3):260-269. Epub 2019 Apr 11.

State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Hepatology Unit and Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.

Background And Aim: Long-term treatment with tenofovir disoproxil fumarate (TDF) has demonstrated suppression of viral replication outside of China. This study aims to assess efficacy, resistance and safety of TDF for up to 240 weeks in Chinese patients with chronic hepatitis B virus (HBV) infection.

Methods: Patients (HBeAg-positive or HBeAg-negative) who were randomised to receive TDF 300 mg or adefovir dipivoxil (ADV) 10 mg once daily in the 48-week double-blind phase (N = 498) were eligible to enter the open-label TDF phase (TDF-TDF and ADV-TDF groups) for additional 192 weeks.

Results: Overall, 457/512 (89.3%) randomised patients completed 240 weeks of treatment. Virological suppression was achieved in 84.5% and 87.9% in HBeAg-positive patients and 89.6% and 89.5% in HBeAg-negative patients in TDF-TDF and ADV-TDF groups, respectively, at week 240. The majority of patients from both groups had normalized alanine transaminase levels. More patients had HBeAg loss (41.7% vs. 36.4%) and HBeAg seroconversion (32.0% vs. 28.3%) in TDF-TDF than in ADV-TDF group, respectively. Only one HBeAg-positive patient in TDF-TDF group had HBsAg loss at week 240. No evidence of resistance to TDF was observed. The incidence of adverse events was similar in both groups (TDF-TDF, 56.4% vs. ADV-TDF, 51.6%). One patient had serum creatinine elevation ≥ 0.5 mg/dL above baseline, and three patients had confirmed grade 3/4 phosphorus abnormalities (< 2 mg/dL).

Conclusion: In Chinese patients with chronic HBV, long-term treatment with TDF showed sustained viral suppression without development of resistance up to 240 weeks. No new safety concerns were found with TDF in this patient population. Clinical Trial Registration ClinicalTrial.gov Identifier NCT01300234; GSK Clinical Study Register 114648.
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http://dx.doi.org/10.1007/s12072-019-09943-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529393PMC
May 2019

Incidence and Etiology of Drug-Induced Liver Injury in Mainland China.

Gastroenterology 2019 06 8;156(8):2230-2241.e11. Epub 2019 Feb 8.

Shanghai Liver Diseases Research Center, 85th Hospital of Nanjing Military Command, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Background & Aims: We performed a nationwide, retrospective study to determine the incidence and causes of drug-induced liver injury (DILI) in mainland China.

Methods: We collected data on a total of 25,927 confirmed DILI cases, hospitalized from 2012 through 2014 at 308 medical centers in mainland China. We collected demographic, medical history, treatment, laboratory, disease severity, and mortality data from all patients. Investigators at each site were asked to complete causality assessments for each case whose diagnosis at discharge was DILI (n = 29,478) according to the Roussel Uclaf Causality Assessment Method.

Results: Most cases of DILI presented with hepatocellular injury (51.39%; 95% confidence interval [CI] 50.76-52.03), followed by mixed injury (28.30%; 95% CI 27.73-28.87) and cholestatic injury (20.31%; 95% CI 19.80-20.82). The leading single classes of implicated drugs were traditional Chinese medicines or herbal and dietary supplements (26.81%) and antituberculosis medications (21.99%). Chronic DILI occurred in 13.00% of the cases and, although 44.40% of the hepatocellular DILI cases fulfilled Hy's Law criteria, only 280 cases (1.08%) progressed to hepatic failure, 2 cases underwent liver transplantation (0.01%), and 102 patients died (0.39%). Among deaths, DILI was judged to have a primary role in 72 (70.59%), a contributory role in 21 (20.59%), and no role in 9 (8.82%). Assuming the proportion of DILI in the entire hospitalized population of China was represented by that observed in the 66 centers where DILI capture was complete, we estimated the annual incidence in the general population to be 23.80 per 100,000 persons (95% CI 20.86-26.74). Only hospitalized patients were included in this analysis, so the true incidence is likely to be higher.

Conclusions: In a retrospective study to determine the incidence and causes of DILI in mainland China, the annual incidence in the general population was estimated to be 23.80 per 100,000 persons; higher than that reported from Western countries. Traditional Chinese medicines, herbal and dietary supplements, and antituberculosis drugs were the leading causes of DILI in mainland China.
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http://dx.doi.org/10.1053/j.gastro.2019.02.002DOI Listing
June 2019

Early steep decline of liver stiffness predicts histological reversal of fibrosis in chronic hepatitis B patients treated with entecavir.

J Viral Hepat 2019 05 14;26(5):576-585. Epub 2019 Feb 14.

Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

It is unknown whether dynamic changes of liver stiffness measurement (LSM) can predict the reversibility of fibrosis. Therefore, we evaluated the utility of LSM changes in predicting histological changes of fibrosis in patients with chronic hepatitis B (CHB) on antiviral therapy. In a prospective cohort of CHB patients treated with entecavir, virological measurement and biochemical measurement along with LSM were measured at baseline and every 6 months. Liver biopsies were conducted at baseline and month 18 of treatment. Fibrosis regression was defined by the following two criteria: (a) Ishak score decrease ≥1 stage, (b) Ishak score decrease ≥1 stage or predominantly regressive by post-treatment PIR classification. The dynamic changes of LSM and its predictive value for histological reversibility were evaluated with piecewise linear mixed-effects model and ROC analysis. We found that at month 18 of antiviral therapy, liver fibrosis was reserved in 86 of 212 (40.6%) CHB patients by Ishak reversal criterion. Overall, a decline in LSM was associated with attenuation of Ishak score. The rate of LSM decline in the first 6 months was significantly faster in patients with fibrosis reversal (ΔLSM%  = -2.19%/month, P = 0.0025; ΔLSM%  = -2.56%/month, P = 0.0004). The predictive model based on baseline FIB-4 and Ishak score as well as baseline LSM, PLT, albumin and their changes during the first 6 months could predict histological reversal (AUROC  = 0.74, 95% CI: 0.67-0.80; AUROC  = 0.81, 95% CI: 0.74-0.87). We conclude that in CHB patients, changes in LSM during the first 6 months of entecavir therapy can predict histological reversibility of liver fibrosis at month 18 of antiviral therapy.
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http://dx.doi.org/10.1111/jvh.13058DOI Listing
May 2019

Neutron scattering in the biological sciences: progress and prospects.

Acta Crystallogr D Struct Biol 2018 Dec 20;74(Pt 12):1129-1168. Epub 2018 Dec 20.

Department of Medicinal Chemistry and Pharmacognosy, Ohio State University College of Pharmacy, 642 Riffe Building, Columbus, OH 43210, USA.

The scattering of neutrons can be used to provide information on the structure and dynamics of biological systems on multiple length and time scales. Pursuant to a National Science Foundation-funded workshop in February 2018, recent developments in this field are reviewed here, as well as future prospects that can be expected given recent advances in sources, instrumentation and computational power and methods. Crystallography, solution scattering, dynamics, membranes, labeling and imaging are examined. For the extraction of maximum information, the incorporation of judicious specific deuterium labeling, the integration of several types of experiment, and interpretation using high-performance computer simulation models are often found to be particularly powerful.
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http://dx.doi.org/10.1107/S2059798318017503DOI Listing
December 2018

Sofosbuvir-velpatasvir for treatment of chronic hepatitis C virus infection in Asia: a single-arm, open-label, phase 3 trial.

Lancet Gastroenterol Hepatol 2019 02 14;4(2):127-134. Epub 2018 Dec 14.

Beijing Friendship Hospital Affiliate of Capital, Beijing, China.

Background: Treatment with combined sofosbuvir and velpatasvir has resulted in high sustained virological response rates in patients chronically infected with hepatitis C virus (HCV) with genotypes 1-6 in clinical trials and real-world settings, but its efficacy and safety has not been assessed in Asia, a region with diverse HCV genotypes.

Methods: In this single-arm, open-label, phase 3 trial, we recruited patients from 38 sites across China, Thailand, Vietnam, Singapore, and Malaysia, who were chronically infected with HCV genotypes 1-6, and were HCV treatment-naive or treatment-experienced, either without cirrhosis or with compensated cirrhosis. Patients self-administered a combined sofosbuvir (400 mg) and velpatasvir (100 mg) tablet once daily for 12 weeks. The primary efficacy endpoint was sustained virological response, defined as HCV RNA less than 15 IU/mL at 12 weeks after completion of treatment (SVR12), assessed in all patients who received at least one dose of study drug. The primary safety endpoint was the proportion of adverse events leading to premature discontinuation of study drug. This trial is registered with ClinicalTrials.gov, number NCT02671500, and is completed.

Findings: Between April 14, 2016, and June 30, 2017, 375 patients were enrolled in the study, of whom 374 completed the full treatment course and one discontinued treatment. Overall, 362 (97% [95% CI 94-98]) of 375 patients achieved SVR12. Among 42 patients with HCV genotype 3b, all of whom had baseline resistance-associated substitutions in NS5A, 25 (89% [95% CI 72-98]) of 28 patients without cirrhosis and seven (50% [23-77]) of 14 patients with cirrhosis achieved SVR12. The most common adverse events were upper respiratory tract infection (36 [10%] patients) and headache (18 [5%] patients). There were no discontinuations due to adverse events. Serious adverse events were reported in three (1%) patients, none of which was judged to be related to sofosbuvir-velpatasvir treatment.

Interpretation: Consistent with data from other phase 3 studies, single-tablet sofosbuvir-velpatasvir for 12 weeks is an efficacious and safe treatment for Asian patients with chronic HCV infection, but might have lower efficacy in those infected with HCV genotype 3b and with cirrhosis.

Funding: Gilead Sciences.
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http://dx.doi.org/10.1016/S2468-1253(18)30343-1DOI Listing
February 2019

Two- and three-dimensional coordination polymers based on zinc(II) and furan-2,5-dicarboxylic acid: structure variation due to metal-to-linker ratio.

Acta Crystallogr C Struct Chem 2018 12 22;74(Pt 12):1719-1724. Epub 2018 Nov 22.

Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, USA.

Two Zn-based coordination polymers (CPs) were synthesized by the hydrothermal method, using Zn(NO)·6HO and furan-2,5-dicarboxylic acid (FDCA) in dimethylformamide (DMF) solvent, at 95 °C. Poly[tetrakis(dimethylazanium) [tetrakis(μ-furan-2,5-dicarboxylato-κO:O)dizinc(II)]], {(CHN)[Zn(CHO)]} or {[DMA][Zn(FDC)]} (DMA = dimethylazanium and FDC = furan-2,5-dicarboxylate), (1), was obtained with a 1:1 molar ratio of Zn and FDCA. It crystallized in the monoclinic space group C2/c. Coordinated by Zn ions, FDC ligands form 2 double-stranded helices propagating along the b axis. The helices are interconnected and extend laterally in the a direction, forming a two-dimensional (2D) sheet-like network. The 2D sheets are stacked along the c direction without interconnections. DMA cations are cocrystallized in (1) and are hydrogen bonded with carboxylate O atoms of the FDC ligands. The hydrogen-bonding pattern consists of R(4) and R(10) motifs alternating in a chain. Poly[bis(dimethylazanium) [bis(μ-furan-2,5-dicarboxylato-κO:κO:κO:κO)bis(μ-furan-2,5-dicarboxylato-κO:κO:κO)dizinc(II)] dimethylformamide 3.08-solvate], {(CHN)[Zn(CHO)]·3.08CHNO} or {[DMA][Zn(FDC)]·3.08DMF}, (2), was obtained with a 1:2 molar ratio of Zn and FDCA. It crystallized in the monoclinic space group P2/c, forming a three-dimensional network. The pores are filled with DMA cations and DMF solvent molecules.
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http://dx.doi.org/10.1107/S2053229618015759DOI Listing
December 2018

GADD45α alleviates acetaminophen-induced hepatotoxicity by promoting AMPK activation.

Cell Mol Life Sci 2019 Jan 27;76(1):129-145. Epub 2018 Aug 27.

Division of Gastroenterology and Hepatology, School of Medicine, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.

As an analgesic and antipyretic drug, acetaminophen (APAP) is commonly used and known to be safe at therapeutic doses. In many countries, the overuse of APAP provokes acute liver injury and even liver failure. APAP-induced liver injury (AILI) is the most used experimental model of drug-induced liver injury (DILI). Here, we have demonstrated elevated levels of growth arrest and DNA damage-inducible 45α (GADD45α) in the livers of patients with DILI/AILI, in APAP-injured mouse livers and in APAP-treated hepatocytes. GADD45α exhibited a protective effect against APAP-induced liver injury and alleviated the accumulation of small lipid droplets in vitro and in vivo. We found that GADD45α promoted the activation of AMP-activated protein kinase α and induced fatty acid beta-oxidation, tricarboxylic acid cycle (TCA) and glycogenolysis-related gene expression after APAP exposure. Liquid chromatography-mass spectrometry (LC-MS) analysis showed that GADD45α increased the levels of TCA cycle metabolites. Co-immunoprecipitation analysis showed that Ppp2cb, a catalytic subunit of protein phosphatase 2A, could interact directly with GADD45α. Our results indicate that hepatocyte GADD45α might represent a therapeutic target to prevent and rescue liver injury caused by APAP.
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http://dx.doi.org/10.1007/s00018-018-2912-yDOI Listing
January 2019

Decentralization, national context and environmental policy performance: a fuzzy set qualitative comparative analysis.

Authors:
Yimin Mao

Environ Sci Pollut Res Int 2018 Oct 7;25(28):28471-28488. Epub 2018 Aug 7.

College of Public Administration, Zhejiang Gongshang University, No.18, Xuezheng Str., Xiasha University Town, Hangzhou, 310018, China.

This study examines the complex relationship between decentralization, national context and environment policy performance with the cross-sectional data from 118 countries. Decentralization is decomposed into three dimensions: political, fiscal and administrative. Both multiple regression analysis and fuzzy set qualitative comparative analysis are adopted. Results show that: (1) political, fiscal and administrative decentralization differ in their impacts on environmental policy performance. (2) There are multiple pathways, constituted by specific configurations of decentralization and context conditions, to high (or low) environmental policy performance. (3) High environmental policy performance occurs most often when a country is fiscally and administratively decentralized and its context is favorable, i.e. advanced economy, good governance and stringent environmental regulations. In this situation, political decentralization seems to be irrelevant to the outcome. (4) Low environmental policy performance occurs most often when a country, without the favorable context mentioned above, become fiscally centralized, regardless of whether political and administrative decentralization is present or not. This study suggests policy makers should keep in mind the contextual fit of decentralization and adopt a configurational thinking in environmental governance.
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http://dx.doi.org/10.1007/s11356-018-2846-9DOI Listing
October 2018

Two furan-2,5-dicarboxylic acid solvates crystallized from dimethylformamide and dimethyl sulfoxide.

Acta Crystallogr C Struct Chem 2018 08 30;74(Pt 8):986-990. Epub 2018 Jul 30.

Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, USA.

Furan-2,5-dicarboxylic acid (FDCA) has been ranked among the top 12 bio-based building-block chemicals by the Department of Energy in the US. The molecule was first synthesized in 1876, but large-scale production has only become possible since the development of modern bio- and chemical catalysis techniques. The structures of two FDCA solvates, namely, FDCA dimethylformamide (DMF) disolvate, CHO·2CHNO, (I), and FDCA dimethyl sulfoxide (DMSO) monosolvate, CHO·CHOS, (II), are reported. Solvate (I) crystallizes in the orthorhombic Pbcn space group and solvate (II) crystallizes in the monoclinic P-1 space group. In (I), hydrogen bonds form between the carbonyl O atom in DMF and a hydroxy H atom in FDCA. Whilst in (II), the O atom in one DMSO molecule hydrogen bonds with hydroxy H atoms in two FDCA molecules. Combined with intermolecular S...O interactions, FDCA molecules form a two-dimensional network coordinated by DMSO.
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http://dx.doi.org/10.1107/S2053229618010471DOI Listing
August 2018

Is it really the "dark side" of herbal medicine?

Sci China Life Sci 2018 09 3;61(9):1118-1119. Epub 2018 Aug 3.

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.

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http://dx.doi.org/10.1007/s11427-018-9351-0DOI Listing
September 2018