Publications by authors named "Lang Lin"

46 Publications

Contamination and ecological risks of steroid metabolites require more attention in the environment: Evidence from the fishing ports.

Sci Total Environ 2021 Oct 6;807(Pt 1):150814. Epub 2021 Oct 6.

Guangdong Provincial Key Laboratory of Fishery Ecology and Environment, Scientific Observation and Research Field Station of Zhujiang Estuary Ecosystem, Guangdong Province, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510300, China. Electronic address:

Due to strong endocrine disrupting effects, steroids in the environment have attracted substantial attention, with studies mostly focusing on the parent steroids. Here, we conducted the first investigation on the contamination profiles, possible sources, mass inventories, and ecological risks of 27 steroids and their metabolites in 15 typical fishing ports in Southeast China. Twelve steroids were detectable in the sediment samples with the total mean concentrations of 4.6-35 ng/g. High proportions of steroid metabolites were measured in the sediments and five metabolites were newly observed. Untreated municipal sewage and aquaculture wastes constitute the possible steroid sources in the studied fishing ports. The total inventories of steroids in fishing ports ranged from 2.1-16 mg/m, with their metabolites being important contributors. The ecological risk analysis indicated high risks across all sampling sites mainly due to the contributions of parent steroids. Furthermore, our results found that progesterone is an acceptable chemical indicator for various steroids in sediments. This study provides the first evidence of steroid metabolites in the marine environment, calling for more studies in environmental behavior and ecotoxicology of steroid metabolites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.150814DOI Listing
October 2021

Randomised clinical trial: dose optimising strategy by NUDT15 genotyping reduces leucopenia during thiopurine treatment of Crohn's disease.

Aliment Pharmacol Ther 2021 Nov 25;54(9):1124-1133. Epub 2021 Sep 25.

Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Introduction: Thiopurine S-methyltransferase (TPTM) is a well known biomarker for thiopurine-induced leucopenia, which has limited value in Asia. Instead, NUDT15 C415T is a promising predictor in Asia.

Aims: To explore whether an optimised strategy based on NUDT15 C415T genotypes affects thiopurine-induced leucopenia, as well as efficacy in Chinese patients with Crohn's disease.

Methods: Patients with Crohn's disease and indications for thiopurines were included from two hospitals in China. They were randomly assigned to either the intervention or the control group. In the intervention group, those with genotype CC received a standard dose (control group), those with CT genotype received 50% of the standard dose, those with TT genotype received alternative drugs. The primary endpoint was thiopurine-induced leucopenia (<3.5 × 10 /L). Secondary outcomes were the incidence of other adverse events and the efficacy for maintaining steroid-free remission at week 36.

Results: The rate of thiopurine-induced leucopenia was lower in the intervention group (n = 52) than in the control group (n = 66) (23.7% vs 32.4%, P = 0.049, RR = 0.73, 95% CI 0.53-1.00). In CT subgroup, the incidence of leucopenia in the intervention group (n = 10) was significantly lower than in the control group (n = 28) (31.3% vs 65.1%, RR = 0.48, 95% CI 0.28-0.84). Neither other adverse events nor treatment efficacy was significantly different between the two groups during follow-up.

Conclusions: Among Chinese patients with Crohn's disease, dose optimisation by NUDT15 C415T reduced the rate of thiopurine-induced leucopenia, without significant influence on efficacy. Using 50% dose reduction for heterozygotes, and alternative drugs for homozygotes, are practicable strategies. Clinical trial number: NCT02929706.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.16600DOI Listing
November 2021

Diabetic wound healing: The impact of diabetes on myofibroblast activity and its potential therapeutic treatments.

Wound Repair Regen 2021 Jul 22;29(4):573-581. Epub 2021 Jun 22.

Department of Surgery, Division of Plastic and Reconstructive Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Diabetes is a systemic disease in which the body cannot regulate the amount of sugar, namely glucose, in the blood. High glucose toxicity has been implicated in the dysfunction of diabetic wound healing, following insufficient production (Type 1) or inadequate usage (Type 2) of insulin. Chronic non-healing diabetic wounds are one of the major complications of both types of diabetes, which are serious concerns for public health and can impact the life quality of patients significantly. In general, diabetic wounds are characterized by deficient chemokine production, an unusual inflammatory response, lack of angiogenesis and epithelialization, and dysfunction of fibroblasts. Increasing scientific evidence from available experimental studies on animal and cell models strongly associates impaired wound healing in diabetes with dysregulated fibroblast differentiation to myofibroblasts, interrupted myofibroblast activity, and inadequate extracellular matrix production. Myofibroblasts play an important role in tissue repair by producing and organizing extracellular matrix and subsequently promoting wound contraction. Based on these studies, hyperglycaemic conditions can interfere with cytokine signalling pathways (such as growth factor-β pathway) affecting fibroblast differentiation, alter fibroblast apoptosis, dysregulate dermal lipolysis, and enhance hypoxia damage, thus leading to damaged microenvironment for myofibroblast formation, inappropriate extracellular matrix modulation, and weakened wound contraction. In this review, we will focus on the current available studies on the impact of diabetes on fibroblast differentiation and myofibroblast function, as well as potential treatments related to the affected pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/wrr.12954DOI Listing
July 2021

Poor sleep quality and its related risk factors among university students.

Ann Palliat Med 2021 Apr;10(4):4479-4485

Department of Oncology, Taizhou Municipal Hospital, Taizhou, China.

Background: Poor sleep quality is a major health problem worldwide. In universities, poor sleep quality can effect student's ability to study and have a serious impact on their psychological and physical well-being. The aim of this study was to explore the quality of sleep among university students and identify risk factors associated with poor sleep quality.

Methods: A cross-sectional study was conducted and the Pittsburgh sleep quality index scale was used to measure sleep quality. The overall score of the PSQI ranges from 0 to 21, with a score of 4 or less indicating good sleep quality, a score of 5-10 indicating fairly good sleep quality, 11-15 indicating fairly bad sleep quality, and a score of 16-21 indicating poor sleep quality.

Results: A total of 1,317 subjects were enrolled in the study. Most subjects were female (64.6%) and rural based (69.2%). Low intensity sports activity more than once per week was reported by 81.9% of subjects and 59.8% reported they participated in high-intensity sports more than once a week. In addition, 72.8% of subjects took a nap more than three times per week.

Conclusions: We found that physical activity and taking a nap may be important factors in improving sleep quality and preventing sleep disorders among university students.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/apm-21-472DOI Listing
April 2021

Occurrence, bioaccumulation, fate, and risk assessment of novel brominated flame retardants (NBFRs) in aquatic environments - A critical review.

Water Res 2021 Jun 21;198:117168. Epub 2021 Apr 21.

State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Novel brominated flame retardants (NBFRs), which have been developed as replacements for legacy flame retardants such as polybrominated diphenyl ethers (PBDEs), are a class of alternative flame retardants with emerging and widespread applications. The ubiquitous occurrence of NBFRs in the aquatic environments and the potential adverse effects on aquatic organisms have initiated intense global concerns. The present article, therefore, identifies and analyzes the current state of knowledge on the occurrence, bioaccumulation, fates, and environmental and health risks of NBFRs in aquatic environments. The key findings from this review are that (1) the distribution of NBFRs are source-dependent in the global aquatic environments, and several NBFRs have been reported at higher concentrations than that of the legacy flame retardants; (2) high bioaccumulative properties have been found for all of the discussed NBFRs due to their strong hydrophobic characteristics and weak metabolic rates; (3) the limited information available suggests that NBFRs are resistant to biotic and abiotic degradation processes and that sorption to sludge and sediments are the main fate of NBFRs in the aquatic environments; (4) the results of ecological risk assessments have indicated the potential risks of NBFRs and have suggested that source areas are the most vulnerable environmental compartments. Knowledge gaps and perspectives for future research regarding the monitoring, toxicokinetics, transformation processes, and development of ecological risk assessments of NBFRs in aquatic environments are proposed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.watres.2021.117168DOI Listing
June 2021

Characteristics of expanded polystyrene microplastics on island beaches in the Pearl River Estuary: abundance, size, surface texture and their metals-carrying capacity.

Ecotoxicology 2021 Oct 9;30(8):1632-1643. Epub 2021 Jan 9.

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Innovation Academy of South China Sea Ecology and Environmental Engineering, Chinese Academy of Sciences, Guangzhou, 510301, China.

While expanded polystyrene (EPS) microplastics have been widely recognized as one of the most important components of plastic litter in the intertidal zones of the global ocean, our understanding of their environmental fate on island beaches is insufficient. In this study, we intended to reveal that the latest EPS microplastic pollution status on 5 island beaches in the Pearl River Estuary, China, by comprehensively assessing the abundance, distribution, size, surface texture and carrying capacity of heavy metals (Cd, As, Cr, Ni, Cu, Pb, Mn, Fe, Al). High level of EPS microplastic abundance ranged from 328 to 82,276 particles m was found, with the highest abundance at Guishan Island and the lowest at Dong'ao Island. Spatial distribution of EPS microplastic abundance was significantly different among different islands. EPS microplastics in the size range of 1-2 mm were the most abundant. The content of heavy metals in EPS microplastics collected on the beaches was greater than that in the new EPS products. The average concentrations of heavy metals in EPS microplastics from 5 islands are Cd (0.27 ± 0.19 μg g), As (5.50 ± 3.84 μg g), Cr (14.9 ± 8.25 μg g), Cu (15.0 ± 7.66 μg g), Ni (17.2 ± 17.6 μg g), Pb (24.8 ± 7.39 μg g), Mn (730 ± 797 μg g), Fe (8340 ± 4760 μg g), and Al (9624 ± 6187 μg g), respectively. The correlation between heavy metals in EPS microplastics and sediments was better than that between heavy metals in EPS microplastics and seawater. The study results indicated that EPS microplastics could act as a carrier for the transport of heavy metals, which might pose a threat to biological and human health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10646-020-02329-7DOI Listing
October 2021

Nanoscale assembly line composed of dual DNA-machines enabling sensitive microRNA detection using upconversion nanoparticles probes.

J Pharm Biomed Anal 2021 Feb 25;195:113842. Epub 2020 Dec 25.

The Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, PR China. Electronic address:

DNA machines are smart artificial devices that perform well-organized DNA hybridization reactions or nanoscale mechanical movements. Herein, a nanoscale assembly line composing of dual DNA machines is meticulously designed by coupling a catalytic hairpin assembly (CHA)-based machine with a 3D DNA walker machine. Equipped with upconversion nanoparticles (UCNPs) as signal tags, the dual DNA machines-based assembly line (DDMAL) can efficiently amplify the fluorescent signal of target recognition event, enabling sensitive detection of microRNA (miRNA). In detail, once activated by target miRNA-21, the CHA machine is initiated to constantly produce a single-stranded DNA (named binding DNA) via the strand displacement reaction. The binding DNA as a trigger factor can initiate the DNA walker machine by linking a walking strand DNA with an anchor strand DNA immobilized on the surface of magnetic beads (MBs). The movement of walking strand on the surface of MBs is then driven by Mn-dependent DNAzyme formed through the hybridization of walking strand with a UCNPs-linked substrate strand. The DNAzyme-catalyzed cleavage of substrate strand is accompanied by the release of numerous UCNPs from MBs. By measuring the fluorescent signal of released UCNPs after the magnetic separation, target miRNA-21 can be detected by the DDMAL system in a linear range from 1.0 fM to 10 nM, with a limit of detection (LOD) of 0.62 fM (3σ). Moreover, the practicability of DDMAL system was demonstrated by using it to evaluate the expression levels of miRNA-21 in cell lines and assay miRNA-21 in human serum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpba.2020.113842DOI Listing
February 2021

Mechanical circulatory support following out-of-hospital cardiac arrest: Insights from the National Cardiogenic Shock Initiative.

Cardiovasc Revasc Med 2020 Dec 22. Epub 2020 Dec 22.

Henry Ford Hospital, Detroit, MI, United States of America.

Background: Evidence is limited regarding the role of mechanical circulatory support (MCS) in patients with acute coronary syndromes (ACS) complicated by cardiogenic shock (CGS). In particular, the role of MCS in patients with out-of-hospital cardiac arrest (OHCA) is unknown.

Methods: The National Cardiogenic Shock Initiative (NCSI) is a multicenter United States registry of patients with ACS complicated by CGS treated with MCS. We compared the rate of survival to hospital discharge among patients with OHCA, in-hospital cardiac arrest (IHCA), or no cardiac arrest. We subsequently used multivariable analyses to determine independent predictors of OHCA survival.

Results: Survival to hospital discharge occurred in 85.7% (42/49) of OHCA, 72.4% (50/69) of IHCA, and 74.5% (111/149) of non-cardiac arrest patients. By multivariable analysis, pre-procedural predictors of survival included younger age, female sex, fewer diseased vessels, left anterior descending coronary artery culprit, lower troponin, higher lactate, and delayed initiation of MCS. Procedural and post-procedural predictors of survival included fewer vessels treated, complete revascularization, higher post-MCS cardiac power output, and fewer inotropic medications required.

Conclusions: This study demonstrates that excellent outcomes may be achieved following OHCA when MCS is employed for patients appropriately selected by prognostic demographic, anatomic, and health status characteristics. A larger study population, currently being enrolled, is needed to validate the observation further.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carrev.2020.12.021DOI Listing
December 2020

Targeted versus universal tuberculosis chemoprophylaxis in 1968 patients with inflammatory bowel disease receiving anti-TNF therapy in a tuberculosis endemic region.

Aliment Pharmacol Ther 2021 02 12;53(3):390-399. Epub 2020 Dec 12.

Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China.

Background: Anti-tumour necrosis factor (anti-TNF) therapy increases the risk of tuberculosis (TB). Given limitations of screening techniques, it remains uncertain if patients receiving anti-TNF in TB endemic regions should be screened for latent infection with chemoprophylaxis restricted to those with proven infection, or if all patients should receive chemoprophylaxis.

Aims: To compare the incidence of active TB with infliximab (IFX) following targeted and universal TB chemoprophylaxis, and to determine the rates of adverse events (AE) related to TB chemoprophylaxis METHODS: A multi-centre retrospective cohort study was performed at 18 hospitals in China of 1968 adult patients with IBD receiving IFX from 2009 to 2017. TB screening prior to IFX was performed with chest X-ray and/or computed tomography [CT] and immune reactivity testing (interferon-γ release assay and/or tuberculin skin test). Patients were followed-up for a minimum of 3 months after IFX discontinuation, or until last hospital visit if IFX therapy was ongoing. Targeted strategy was defined as TB chemoprophylaxis only for patients with a positive latent TB screen, with universal strategy defined as TB chemoprophylaxis for all patients.

Results: Mean follow-up was 1.07 ± 0.87 years with a total follow-up of 2102 patient-years. There were 1433 patients in the targeted and 483 patients in the universal TB chemoprophylaxis groups, with no significant difference in the incidence rates of active TB between groups (673.3 per 100 000 population per year vs 891.5 per 100 000 population per year, P = 0.60). In the targeted group, 55/1433 patients received TB chemoprophylaxis compared with 483/483 in the universal group, with significantly fewer AEs related to TB chemoprophylaxis in the targeted compared to the universal group (0.35% (5/1433) vs 6.8% (33/483), P < 0.05).

Conclusions: In this study of patients receiving IFX in a TB endemic area, universal chemoprophylaxis was not associated with a reduced risk of active TB when compared to a targeted chemoprophylaxis strategy, and AEs were more common. This supports the use of targeted TB chemoprophylaxis when anti-TNF therapy is initiated in TB endemic regions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.16130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839545PMC
February 2021

Long non-coding RNA SNHG1 regulates rheumatoid synovial invasion and proliferation by interaction with PTBP1.

Int Immunopharmacol 2021 Jan 18;90:107182. Epub 2020 Nov 18.

Division of Rheumatology, Department of Internal Medicine, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address:

Fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) present proliferative and aggressive cell phenotype. RA-FLSs are the essential effector cells that lead to symptoms like synovial inflammation and joint destruction. Currently, the cause of RA-FLSs involving in the pathological process of RA remains unknown. Accumulate researches have demonstrated that lncRNAs may play a critical role in regulating the biological behaviors of RA-FLSs, but the mechanism is still unclear. Here, we found that lncRNA small nucleolar RNA host gene 1 (SNHG1) is up-regulated in RA-FLSs compared with FLSs from trauma arthritis and osteoarthritis patients. The results suggest that SNHG1 in RA-FLSs helps to sustain the cellular functions of proliferation, migration and invasion. Furthermore, the regulation mechanism depends on the interaction between SNHG1 and polypyridine tract-binding protein 1 (PTBP1). This interaction influences PTBP1 expression that participates in the regulation of RA-FLSs biological behaviors. Our results suggest that up-regulated SNHG1 of RA-FLSs may contribute to synovial aggression and disease progression in RA and be favourable for RA treatment target RA-FLSs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2020.107182DOI Listing
January 2021

Low level of microplastic contamination in wild fish from an urban estuary.

Mar Pollut Bull 2020 Nov 10;160:111650. Epub 2020 Sep 10.

Marine Environmental Testing Center, South China Sea Institute of Oceanology, Innovation Academy of South China Sea Ecology and Environmental Engineering, Chinese Academy of Sciences, Guangzhou 510301, China.

Microplastic accumulation in estuarine environments is considered the dominant input of land-based plastics into the oceans. In this study, the level of microplastic contamination was evaluated in 26 species of wild fish from the Pearl River Estuary, South China. Results showed that microplastics abundance ranged from 0.17 items individual (Boleophthalmus pectinirostris & Acanthogobius flavimanus) to 1.33 items individual (Plectorhynchus cinctus) among different species. The distribution of microplastic abundance in the gills and gastrointestinal tracts was not significantly different. Microplastics in gills are strongly related to the filtration area of gills in 15 fish species. Fibers were the dominant shapes accounting for 93.45% of the total shapes. The majority of microplastics were <3 mm in size. The most common polymer composition was polyethylene terephthalate (38.2%) and the most common color was black (30.36%). The findings of this study provide baseline data for microplastic contamination in wild fish from an urban estuary.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.marpolbul.2020.111650DOI Listing
November 2020

Different structural transitions of rapidly supercooled tantalum melt under pressure.

Phys Chem Chem Phys 2020 Aug;22(32):18078-18090

School of Computational Science & Electronics, Hunan Institute of Engineering, Xiangtan 411104, China.

Molecular dynamics (MD) simulations have been performed to study the effects of pressure (P) on the crystallization of tantalum (Ta) under different pressures from [0, 100] GPa. The average potential energy of atoms in the system, the pair distribution function and largest standard cluster analysis (LSCA) have been employed to analyze the structure evolution. It was found that the solidified state at 100 K changes from the complex crystal (β-Ta) through the body-centered cubic (bcc) crystal (α-Ta) to the hexagonal close-packed (hcp) crystal with increasing pressure. At P ≤ 3 GPa, the favorable state is β-Ta, which is composed of Z12, Z14 and Z15 atoms, and crystallization starts at the same temperature of crystallization (Tc = 1897 K), while there is a stochastic relationship between the crystallinity and pressure. At P ∈ [3, 57.5] GPa, the melt is always crystallized into rather perfect α-Ta, and Tc is nearly linear to pressure. However, when P > 57.5 GPa, a quite perfect bcc crystal is first formed and then transforms to a hcp crystal via a solid-solid (bcc-hcp) phase transition. Moreover, if the new hcp atoms formed in the bcc stage are arranged in regular grains, the bcc-hcp transition would take a multiple-intermediate-state pathway else, a single-intermediate-state pathway is the possibilty. Additionaly, the parameter δs readily reflects the crystallinity of the β-Ta, and smaller the value of δs, higher is the crystallinity of the β-Ta. Finally, during the bcc-hcp transition under high pressure, the volume reduction is due to the rearrangement of atoms rather than the reduction in the atomic radius; a slight increase in the number of nearest neighboring pairs results in a significant increase of the system energy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cp01432jDOI Listing
August 2020

Spatial variation of floatable plastic debris and microplastics in the Pearl River Estuary, South China.

Mar Pollut Bull 2020 Sep 15;158:111383. Epub 2020 Jul 15.

Greenpeace East Asia, Hong Kong, China.

The estuaries of populated catchments have been documented as hotspots of plastic pollution. In this study, microplastics (0.355-5.0 mm) and large plastic debris (>5.0 mm) of surface water collected from the Inner Lingding Bay of the Pearl River Estuary (PRE) were quantified and categorized according to their size, shape, colour and composition. Both microplastics and large plastic debris were detected at all sampling sites with mean abundances of 2.376 ± 0.700 n/m and 0.110 ± 0.039 n/m, respectively. Microplastics constitute 95.4% of the total abundance by number. The average microplastic concentration in the inner PRE was almost 3.5 times higher than that in the central PRE, indicating a positive correlation between plastic concentration and proximity to the river mouth. This result reveals the important role of rivers in transporting plastic debris from land to the oceans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.marpolbul.2020.111383DOI Listing
September 2020

Microplastic pollution around remote uninhabited coral reefs of Nansha Islands, South China Sea.

Sci Total Environ 2020 Jul 1;725:138383. Epub 2020 Apr 1.

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Innovation Academy of South China Sea Ecology and Environmental Engineering, Chinese Academy of Sciences, Guangzhou 510301, China. Electronic address:

Microplastic (MP) pollution is a growing environmental problem in the global oceans. However, there is relatively little evidence of the extent of MP pollution around remote islands, such as coral reefs, in the open ocean. In this study, we conducted a large-scale investigation of MP pollution in the surface waters around the remote uninhabited coral reefs of Nansha Islands in South China Sea. Microplastics were widespread in the surface waters with an average abundance of 0.0556 ± 0.0355 items/m, although this varied among the coral reefs. The MPs were predominantly composed of polypropylene (PP) and polyethylene (PE), and > 70% of them were <3 mm in size. Fragments and fibers comprised the most common MP types. The similarity between macro plastic and MP compositions provided evidence for the tracing of MP sources in the study area. The main pollutants (transparent PP fibers and PE fibers) around these remote coral reefs may originate from fishing gear abrasions. The plastic waste released from nearby residential islands and high-intensity fishing activities around Nansha Islands likely represented important local sources. Overall, the abundance of MPs found in the surface waters surrounding these remote coral reefs in the South China Sea was relatively low; however, these levels of MP pollution should not be disregarded given the importance of coral reef ecosystems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.138383DOI Listing
July 2020

Microplastics in mangrove sediments of the Pearl River Estuary, South China: Correlation with halogenated flame retardants' levels.

Sci Total Environ 2020 Jul 3;725:138344. Epub 2020 Apr 3.

CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China; Innovation Academy of South China Sea Ecology and Environmental Engineering, Chinese Academy of Sciences, Guangzhou 510301, China. Electronic address:

Marine microplastic pollution of intertidal mangrove ecosystem is a matter of concern. However, the relationship between microplastic distribution and other pollutants such as halogenated flame retardants (HFRs) is unknown. In this study, forty-eight sediment samples were collected from three mangrove wetlands of the Pearl River Estuary (PRE), South China to investigate the distribution of microplastic and discuss the possible relationship between HFRs and microplastic abundance in mangrove sediments. The abundance of microplastic in mangrove sediments from the PRE ranged from 100 to 7900 items·kg dry weight (dw), with an average of 851 ± 177 items·kg dw, which was at a relatively higher level compared to other regions worldwide. The highest abundance of microplastic was observed in Shenzhen mangrove sediments. The abundance of microplastic was significantly and positively correlated with population density and gross domestic product of the PRE. The microplastics with size <500 μm were predominant in mangrove sediments, accounting for a proportion of 69.4% in all microplastic samples. Polypropylene-polyethylene copolymer, green/black, and fibers/fragments were the dominant type, color and shape in all microplastic samples, respectively. The correlation between HFRs and microplastic abundance demonstrated that polybrominated diphenyl ethers, decabromodiphenyl ethane, 1,2-bis(2,4,6-tribromophenoxy)ethane and hexabromocyclododecane may have the same pollution source as microplastics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.138344DOI Listing
July 2020

Polyoxometalate-based room-temperature phosphorescent materials induced by anion-π interactions.

Dalton Trans 2020 Mar 4;49(11):3408-3412. Epub 2020 Mar 4.

CAS Key Laboratory of Design and Assembly of Functional Nanostructures, and Fujian Key Laboratory of Nanomaterials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.

A series of host-guest materials containing polyoxometalate anions and lanthanide-organic layers have been synthesized and structurally characterized. By anion-π interactions between the anions and the π-acidic naphthalenediimide moieties, the materials emit strong red room-temperature phosphorescence and exhibit reversible photochromism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0dt00159gDOI Listing
March 2020

A bi-polyoxometallate-based host-guest metal-organic framework.

Chem Commun (Camb) 2020 Feb;56(16):2503-2506

CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Key Laboratory of Nanomaterials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, P. R. China.

Anionic POMs prefer to bond with positive metal cations instead of neutral or negative organic ligands. Therefore, it is challenging to synthesize POM-based MOFs, let alone bi-POM-based host-guest MOFs. In this work, an unprecedented bi-POM-based host-guest MOF, Na[Ni(enMe)2]4[Ni(enMe)2(H2O)2]2{[Ni6(μ3-OH)3(enMe)3 (SIP)1.5(B-α-PW9O34)]2[H3PNiW11O40]}·5enMe·33H2O (1), with Ni6-capped [PW9O34] as the node of the host framework and Keggin-type [PNiW11O40] units as the guest was synthesized. 1 showed excellent chemical stability towards aqueous solutions of pH 2-12 at both ambient and boiling temperature, providing opportunities for its application in fresh water harvesting from air.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9cc09008hDOI Listing
February 2020

Is tailored therapy based on antibiotic susceptibility effective ? a multicenter, open-label, randomized trial.

Front Med 2020 Feb 3;14(1):43-50. Epub 2020 Jan 3.

The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.

An effective eradication therapy of Helicobacter pylori (H. pylori) should be used for the first time. In this study, we assessed whether tailored therapy based on antibiotic susceptibility testing is more effective than traditional therapy. We also evaluated the factors that cause treatment failure in high-resistance areas. For this multicenter trial, we recruited 467 H. pylori-positive patients. The patients were randomly assigned to receive tailored triple therapy (TATT), tailored bismuth-containing quadruple therapy (TABQT), or traditional bismuth-containing quadruple therapy (TRBQT). For the TATT and TABQT groups, antibiotic selection proceeded via susceptibility testing using an agar-dilution test. The patients in the TRBQT group were given amoxicillin, clarithromycin, esomeprazole, and bismuth. Successful eradication was defined as a negative C-urea breath test at least eight weeks after the treatment ended. Susceptibility testing was conducted using an agar-dilution test. The eradication rate was examined via intention-to-treat (ITT) and per-protocol (PP) analyses. The clarithromycin, levofloxacin, and metronidazole resistance rates were 26.12%, 28.69%, and 96.79%, respectively. Resistance against amoxicillin and furazolidone was rare. The eradication rates for TATT, TRBQT, and TABQT were 67.32%, 63.69%, and 85.99% in the ITT analysis (P 0.001) and 74.64%, 68.49%, and 91.22% in the PP analysis (P 0.001), respectively. The efficacy of TABQT was affected by clarithromycin resistance, and bismuth exerted a direct influence on TATT failure. TABQT was the most efficacious regimen for use in high-resistance regions, especially among clarithromycin-susceptible patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11684-019-0706-8DOI Listing
February 2020

Postsynthetic Modification of ZIF-8 Membranes via Membrane Surface Ligand Exchange for Light Hydrocarbon Gas Separation Enhancement.

ACS Appl Mater Interfaces 2020 Jan 13;12(3):3893-3902. Epub 2020 Jan 13.

Chemical Engineering, School for Engineering of Matter, Transport and Energy , Arizona State University , Tempe , Arizona 85287 , United States.

The ability to tailor the pore structure of metal-organic framework (MOF) membranes enables synthesis of new or modified MOF membranes with enhanced separation characteristics. This work employs a modified version of solvent-assisted ligand exchange, termed membrane surface ligand exchange (MSLE), to modify the pore structure of zeolitic imidazolate framework-8 (ZIF-8) membranes. This paper is the first to perform a time-based, ex situ characterization and gas permeation study of ZIF-8 MSLE with 5,6-DBIM (DBIM, dimethylbenzimidazole) to effectively narrow the ZIF-8 pores, enhance light hydrocarbon gas-phase separations, and give insight into the exchange mechanism with respect to time and temperature. The results show that relatively fast exchange kinetics occur mainly at the outer surface of the ZIF-8 membrane during the initial 30 min of exchange and enables significant (40-70%) increases in propylene/propane selectivity with minimal (10-20%) propylene permeance losses for the modified ZIF-8 membranes. We postulate as the reaction time proceeds, the ligand-exchange rate slows as the DBIM linker diffuses into the ZIF-8 membrane beyond the external surface, exchanges with the original linker, disrupts the original framework's crystallinity, and then increases long-range order/crystallinity as the reaction proceeds. The H/C separation factor increases with increased 5,6-DBIM content in the ZIF-8 framework which is facilitated by increased MSLE time and reaction temperature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.9b19964DOI Listing
January 2020

Occurrence of microplastics in gastrointestinal tracts and gills of fish from Beibu Gulf, South China Sea.

Environ Pollut 2020 Mar 14;258:113734. Epub 2019 Dec 14.

CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Innovation Academy of South China Sea Ecology and Environmental Engineering, Chinese Academy of Sciences (CAS), Guangzhou 510301, China. Electronic address:

Microplastics are widespread across the global oceans, yet the potential risks of the ubiquitous environmental contaminant to marine organisms has been less known. Accumulation of microplastics and associated contaminants in marine fish, may pose adverse impacts to human health via seafood consumption. This study evaluated microplastic contamination in 24 fish species collected from Beibu Gulf, one of the world's largest fishing grounds in South China Sea. Microplastics were detected in 12 fish species at an abundance of 0.027-1.000 items individual and found in fish stomach, intestines and gills with the count percentage of 57.7%, 34.6% and 7.7%, respectively. Transparent fibers were observed as the predominant microplastics, which might be ingested accidently by fish or transferred through other animals at lower trophic levels. Majority of microplastics were identified as polyester (44%) and nylon (38%), whereas polypropylene (6%), polyethylene (6%), and acrylics (6%) were also found. Relatively, higher microplastic abundances were found in demersal fish compared to the pelagic species. Overall, the abundance of microplastics was documented as relatively low in the commercial fish collected from the open water of Beibu Gulf, South China Sea.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2019.113734DOI Listing
March 2020

Microplastic accumulation in fish from Zhanjiang mangrove wetland, South China.

Sci Total Environ 2020 Mar 4;708:134839. Epub 2019 Nov 4.

CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Institution of South China Sea Ecology and Environmental Engineering, Chinese Academy of Sciences (CAS), Guangzhou 510301, China. Electronic address:

Microplastics (MPs) are widespread in marine and estuarine environments, but the contamination of MPs in mangrove wetlands is relatively unknown. Here, we quantify the presence of MPs in fish collected from Zhanjiang mangrove wetland, the largest mangrove in South China, which provide baseline data on MPs accumulation in fish in mangrove environment as the first evidence in China. MPs were found in 30 out of 32 fish species at an average abundance of 2.83 ± 1.84 items individual, ranged from 0.6 to 8.0 items individual in each species. MPs were detected in gills, stomach and intestine, and not found in muscles and livers. Positive relationship was found between MPs abundance and body length or weight of mangrove fish. The dominant polymers identified by micro-FTIR were polyethylene, polyethylene terephthalate, polypropylene and cellophane. MPs consisted primarily of fibers and with the prominent size range of 0.02-1 mm. The body sizes, living habitats and feeding habits of fish are important factors affecting MPs accumulation in different fish species. This study revealed the wide presences of MPs in fish species within a mangrove wetland.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2019.134839DOI Listing
March 2020

Immunomodulatory Effects of Phosphorylated Polysaccharides in Immunosuppressed Mice.

Molecules 2019 Nov 15;24(22). Epub 2019 Nov 15.

Department of Veterinary Medicine, Southwest University, Rongchang, Chongqing 402460, China.

This research aimed to investigate the immunomodulatory effects of phosphorylated polysaccharides (pRCPS) in immunosuppressed mice, improving their cellular and humoral immune function. Our results showed that pRCPS increased serum immunoglobulin (IgG, IgA, IgM) concentrations significantly, enhanced splenocyte proliferation, and the thymus and spleen indices. pRCPS also promoted phagocytosis in peritoneal macrophages and enhanced cytokine (IFN-γ, IL-2, -4, -5, -6, and -10) serum levels. Importantly, pRCPS increased the proportions of selected T cell subpopulations (CD3, CD4, and the CD4 to CD8 ratio). Our results revealed that phosphorylation of the polysaccharides promoted their immune-enhancing effects. Thus, pRCPS can enhance cellular and humoral immunity and could be used as an immune-enhancing agent to overcome cyclophosphamide (CY)-induced immunosuppression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules24224150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891547PMC
November 2019

Uptake, Elimination, and Biotransformation Potential of a Progestagen (Cyproterone Acetate) in Tilapia Exposed at an Environmental Concentration.

Environ Sci Technol 2019 06 30;53(12):6804-6813. Epub 2019 May 30.

The Environmental Research Institute, MOE Key Laboratory of Theoretical Chemistry of Environment , South China Normal University , Guangzhou 510006 , P. R. China.

Although the distribution of progestagens in aquatic environments has been widely reported, details on their uptake, elimination, and biotransformation in fish have received little attention. This study investigated the uptake, elimination, and biotransformation potential of a progestagen, cyproterone acetate (CPTA), in Nile tilapia ( Oreochromis niloticus) exposed to an environmentally relevant concentration under semistatic regimes. CPTA in tilapia tissues followed a similar pattern, reaching a concentration plateau within 4 days of exposure, and dropping to below limits of quantitation within 4 days of elimination. The calculated steady-state bioconcentration factors suggest a low bioconcentration potential of CPTA in juvenile tilapia. Results of enzymatic hydrolysis treatments revealed that no conjugates of CPTA were present in tissues, but conjugated biotransformation products of CPTA were found in bile, liver, and muscle. Most CPTA entered tissues and then was biotransformed into seven different products by phase I and phase II metabolism. The concentrations of endogenous cortisol were significantly influenced by CPTA in plasma and liver during the uptake period. These findings suggest that biotransformation products of CPTA should be considered for the assessment of the bioconcentration potential and ecological effects of progestagens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.9b02891DOI Listing
June 2019

Topologically close-packed characteristic of amorphous tantalum.

Phys Chem Chem Phys 2018 Nov;20(44):28088-28104

College of Computer Science and Electronic Engineering, Hunan University, Changsha 410082, China.

The structural evolution of tantalum (Ta) during rapid cooling was investigated by molecular dynamics simulation, in terms of the system energy, the pair distribution function and the largest standard cluster analysis. It was found that the critical cooling rate for vitrification was about R ≥ 0.25 K ps-1, two orders lower than other metals (such as Au, Ag, Al, Zr and Zn) and that the meta-stable σ phase (β-Ta) not only appears on the pathway from liquid to the stable body-centred cubic crystal, but is also easily obtained at room temperature as a long-lived metastable phase with some probability. The most interesting point is that the liquid, amorphous and β-Ta phases share a nontrivial structural homology; the intrinsic topologically close-packed (TCP) structures in liquids are inherited and developed in different ways, resulting in amorphous or crystalline solids, respectively. With highly local packing fractions and geometrical incompatibility with the global close-packed (such as hcp, fcc and bcc) crystals, TCP structures inevitably result in structural heterogeneity and favour vitrification. As a superset of icosahedrons, TCP structures are ubiquitous in metallic melts, and just before the onset of crystallization reach their maximal number, which is much bigger in Ta than in other poor-GFA metals; so we argue that the strong forming ability of TCP local structures significantly enhances the glass forming ability of pure metals. These findings open up a new perspective that could have a profound impact on the research into metallic glasses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8cp05897kDOI Listing
November 2018

Sorption and desorption of phenanthrene on biodegradable poly(butylene adipate co-terephtalate) microplastics.

Chemosphere 2019 Jan 3;215:25-32. Epub 2018 Oct 3.

CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China. Electronic address:

Biodegradable plastics, as alternatives to conventional plastics, are increasingly used, but their interactions with organic pollutants are still unknown. In this study, the sorption and desorption behaviors on a type of biodegradable plastic-poly(butylene adipate co-terephtalate) (PBAT) were investigated, and at the same time two types of conventional plastics-polyethylene (PE and PE) and polystyrene (PS) were used for comparison. Phenanthrene (PHEN) was chosen as one of representative organic pollutants. Results indicated that the sorption and desorption capacities of PBAT were not only higher than those of the other types of microplastics, but also higher than those of carbonaceous geosorbents. The surface area normalized results illustrated that sorption and desorption of the microplastics were positively correlated with their abundance of rubbery subfraction. The sorption kinetic results showed that the sorption rates of PBAT and PE were higher than PE and PS. The effects of water chemistry factors including salinity, dissolved organic matter and Cu ion on the sorption process displayed the same trend, but the degrees of influence on the four microplastics differed. The degrees of influence were mainly dependent on the abundance of rubbery subfraction for microplastics. These findings indicate that the biodegradable poly(butylene adipate co-terephtalate) microplastics are actually stronger vectors than the conventional microplastics, and crystallization characteristics of the microplastics have great influences on the vector effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2018.09.173DOI Listing
January 2019

Inhibition of Suv39H1 enhances transgenic IFNα-2b gene expression in Bcap-37 cells.

Anim Biotechnol 2019 Oct 4;30(4):358-365. Epub 2018 Sep 4.

State Key Laboratory of Subtropical Bioresource Conservation and Utilization at Guangxi University , Guangxi , China.

The low expression of exogenous transferred gene limited the application of transgenic animal technology. Suppressor of variegation 3 ∼ 9 homolog 1(SUV39H1) gene plays a prominent role on repressive heterochromatin and transcription. To understand if exogenous transgenic gene expression was affected by SUV39H1 epigenetic modification, in this paper, the effective shRNA fragments targeting SUV39H1 gene were first screened, their roles on expression of exogenous transgenic genes were determined by using Bcap-37 cell line with stable expressing IFNα-2b gene as a model, the preliminary regulation mechanism of SUV39H1 gene was investigated. The results showed that the designed shRNA1/2 fragments of SUV39H1 gene had an obvious inhibition effect on the expression of SUV39H1 gene, reached 53.07 and 31.28%, respectively by qRT-PCR analysis. Compared with the control group, the expression of IFNα-2b gene in transgenic Bcap-37 cells infected with shRNA1 and 2 viruses significantly increased by 96.25 and 121.08%, respectively ( 0.05). In addition, the expression of DNMT1, HDAC1 and G9a gene in the shRNA infected cells reduced significantly, and the expression of the HAT1 gene increased significantly ( 0.05). The above results indicated that the expression of exogenous transgenic gene could be promoted by suppressing SUV39H1 gene at the cell level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10495398.2018.1500373DOI Listing
October 2019

Occurrence and distribution of microplastics in an urban river: A case study in the Pearl River along Guangzhou City, China.

Sci Total Environ 2018 Dec 5;644:375-381. Epub 2018 Jul 5.

CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.

Microplastics, as emerging contaminants in the global environment, have become a cause for concern for both academics and the public. The present understanding of microplastic pollution is primarily focused on marine environments, and less attention has been given to freshwater environments, in particular, to urban rivers. In this study, microplastics were sampled from surface water and sediments in 14 sites located in the lower course of the Pearl River. These sampling sites are located along Guangzhou of South China, with built-up areas being the dominant land use. The abundances of microplastics in surface water and sediments ranged from 379 to 7924 items·m and 80 to 9597 items·kg, respectively. Polyethylene and polypropylene were the common types of microplastics, together accounting for 64.3% and 73.8% of surface water and sediment samples, respectively. Fibers were the dominant microplastic shapes in both water and sediment samples. The abundances of microplastics varied in surface water and sediments with each site, which might be affected by multiple factors. Our results indicated that wastewater treatment plants (WWTP) could reduce microplastics from municipal sewage which was finally discharged into the Pearl River along Guangzhou.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2018.06.327DOI Listing
December 2018

Correlations between microbial communities in stool and clinical indicators in patients with metabolic syndrome.

World J Clin Cases 2018 Apr;6(4):54-63

Department of Research Service, Zhiyuan Medical Inspection Institute CO., LTD, Hangzhou 310030, Zhejiang Province, China.

Aim: To analyze the bacterial community structure and distribution of intestinal microflora in people with and without metabolic syndrome and combined these data with clinical indicators to determine relationships between selected bacteria and metabolic diseases.

Methods: Faecal samples were collected from 20 patients with metabolic syndrome and 16 controls at Cangnan People's Hospital, Zhejiang Province, China. DNA was extracted and the V3-V4 regions of the 16S rRNA genes were amplified for high throughput sequencing. Clear reads were clustered at the 97% sequence similarity level. α and β diversity were used to describe the bacterial community structure and distribution in patients. Combined with the clinical indicators, further analysis was performed.

Results: , , , , were the dominant phyla, and , and was the top three genera in faecal samples. α diversity analysis showed that the species richness of metabolic syndrome samples (group D) was significantly higher than the control (group C) ( < 0.05), and the microbial diversity of group C was greater than that of group D. According to the principal co-ordinates analysis, the samples of group C clustered more tightly, indicating that the distribution of bacteria in healthy patients was similar. The correlation analysis showed that alkaline phosphatase was negatively correlated with the abundance of ( < 0.05). There was a negative correlation between low-density lipoprotein and the abundance of ( < 0.05) and a positive correlation between the high-density lipoprotein and the abundance of ( < 0.05). The total protein and the alanine aminotransferase was positively correlated with the abundance of ( < 0.05).

Conclusion: The changes microbial communities can be used as an indicator of metabolic syndrome, and may be a target microorganism in patients with metabolic syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12998/wjcc.v6.i4.54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902506PMC
April 2018

Microplastics in oysters Saccostrea cucullata along the Pearl River Estuary, China.

Environ Pollut 2018 May;236:619-625

Marine Laboratory, Nicholas School of the Environment, Duke University, Beaufort, NC 28516, USA.

As a transitional zone between riverine and marine environments, an estuary plays an important role for the sources, accumulation and transport of microplastics. Although estuarine environments are hotspots of microplastic pollution, the correlation between microplastic pollution and aquatic organisms is less known. Here we investigated microplastic pollution in wild oysters Saccostrea cucullata from 11 sampling sites along the Pearl River Estuary in South China. The microplastic abundances in oysters ranged from 1.4 to 7.0 items per individual or from 1.5 to 7.2 items per gram tissue wet weight, which were positively related to those in surrounding waters. The oysters near urban areas contained significantly more microplastics than those near rural areas. Fibers accounted for 69.4% of the total microplastics in oysters. Microplastic sizes varied from 20 to 5000 μm and 83.9% of which were less than 100 μm. Light color microplastics were significantly more common than dark color ones. Based on the results, oysters are recommended as a biomonitor for the microplastic pollution in estuaries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2018.01.083DOI Listing
May 2018

Combined Detection of NUDT15 Variants Could Highly Predict Thiopurine-induced Leukopenia in Chinese Patients with Inflammatory Bowel Disease: A Multicenter Analysis.

Inflamm Bowel Dis 2017 09;23(9):1592-1599

*Department of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China; †Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China; ‡Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; §Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China; ‖Department of Gastroenterology, Xijing Hospital, the Fourth Military Medical University, Xi'an, China; and ¶Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Background: NUDT15 c.415C>T was a novel genetic marker confirmed in our center for thiopurine-induced leukopenia in Chinese inflammatory bowel disease (IBD). For validation, a large cohort study is needed. Meanwhile, the newly discovered NUDT15 coding variants (c.36_37insGGAGTC and c.52 G>A) have not been studied in patients with IBD. We aimed to further confirm the influence of 3 NUDT15 variants (c.415C>T, c.36_37insGGAGTC, and c.52G>A) on thiopurine-induced leukopenia in Chinese patients with IBD.

Methods: Patients prescribed on thiopurines for at least 2 weeks were recruited from 4 tertiary hospitals. Clinical data were collected. NUDT15 genotypes were determined with polymerase chain reaction-RFLP and sequencing. The interactions between variants and leukopenia were analyzed.

Results: A total of 732 patients were included, 177 (24.3%) of whom developed leukopenia. There were strong associations of NUDT15 c.415C>T, c.36_37insGGAGTC, and c.52G>A with thiopurine-induced leukopenia (P = 1.81 × 10, P = 4.74 × 10 and P = 0.04, respectively), whereas there was no relevance for thiopurine S-methyltransferase genotypes (P = 0.25). The predictive sensitivity of NUDT15 c.415C>T was 49.2%, whereas it increased to 55.4% when combined analysis with c.36_37insGGAGTC and c.52G>A. Notably, not only the homozygotes with NUDT15 c.415C>T but also the heterozygotes both carrying c.415C>T and c.52G>A developed early leukopenia. The median dosage for NUDT15 c.415C>T carriers was significantly lower than that for wild-type (P < 0.001).

Conclusions: We confirmed that NUDT15 c.415C>T, c.36_37insGGAGTC, and c.52G>A variants were risk factors for thiopurine-induced leukopenia. Combined detection of the 3 variants could increase the predictive sensitivity of thiopurine-induced leukopenia and help to distinguish early leukopenia in heterozygote of c.415C>T in Chinese patients with IBD. Treatment monitoring by NUDT15 variants may be promising in individualized therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MIB.0000000000001148DOI Listing
September 2017
-->