Publications by authors named "Guangju Zhao"

36 Publications

Emodin alleviates LPS-induced myocardial injury through inhibition of NLRP3 inflammasome activation.

Phytother Res 2021 Jun 16. Epub 2021 Jun 16.

Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China.

Myocardial injury and cardiovascular dysfunction are serious consequences of sepsis and contribute to high mortality. Currently, the pathogenesis of myocardial injury in sepsis is still unclear, and therapeutic approaches are limited. In this study, we investigated the protective effect of emodin on septic myocardial injury and the underlying mechanism. Lipopolysaccharide (LPS)-induced C57BL/6 mice and cardiomyocytes were used as models of sepsis in vivo and in vitro, respectively. The results showed that emodin alleviated cardiac dysfunction, myocardial injury and improved survival rate in LPS-induced septic mice. Emodin attenuated the levels of inflammatory cytokines and cardiac inflammation induced by LPS. Emodin reduced NOD-like receptor protein 3 (NLRP3) and Gasdermin D (GSDMD) expression in the heart tissue of LPS-induced septic mice. In vitro, emodin alleviated LPS-induced cell injury and inflammation in cardiomyocytes by inhibiting NLRP3 inflammasome activation. In addition, an NLRP3 inhibitor was used to further confirm the function of the NLRP3 inflammasome in LPS-induced myocardial injury. Taken together, our findings suggest that emodin improves LPS-induced myocardial injury and cardiac dysfunction by alleviating the inflammatory response and cardiomyocyte pyroptosis by inhibiting NLRP3 inflammasome activation, which provides a feasible strategy for preventing and treating myocardial injury in sepsis.
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http://dx.doi.org/10.1002/ptr.7191DOI Listing
June 2021

Soil erosion modelling: A bibliometric analysis.

Environ Res 2021 06 31;197:111087. Epub 2021 Mar 31.

State Key Laboratory of Earth Surface Processes and Resource Ecology, Faculty of Geographical Science, Beijing Normal University, Beijing, China; Institute of Land Surface System and Sustainable Development, Faculty of Geographical Science, Beijing Normal University, Beijing, China.

Soil erosion can present a major threat to agriculture due to loss of soil, nutrients, and organic carbon. Therefore, soil erosion modelling is one of the steps used to plan suitable soil protection measures and detect erosion hotspots. A bibliometric analysis of this topic can reveal research patterns and soil erosion modelling characteristics that can help identify steps needed to enhance the research conducted in this field. Therefore, a detailed bibliometric analysis, including investigation of collaboration networks and citation patterns, should be conducted. The updated version of the Global Applications of Soil Erosion Modelling Tracker (GASEMT) database contains information about citation characteristics and publication type. Here, we investigated the impact of the number of authors, the publication type and the selected journal on the number of citations. Generalized boosted regression tree (BRT) modelling was used to evaluate the most relevant variables related to soil erosion modelling. Additionally, bibliometric networks were analysed and visualized. This study revealed that the selection of the soil erosion model has the largest impact on the number of publication citations, followed by the modelling scale and the publication's CiteScore. Some of the other GASEMT database attributes such as model calibration and validation have negligible influence on the number of citations according to the BRT model. Although it is true that studies that conduct calibration, on average, received around 30% more citations, than studies where calibration was not performed. Moreover, the bibliographic coupling and citation networks show a clear continental pattern, although the co-authorship network does not show the same characteristics. Therefore, soil erosion modellers should conduct even more comprehensive review of past studies and focus not just on the research conducted in the same country or continent. Moreover, when evaluating soil erosion models, an additional focus should be given to field measurements, model calibration, performance assessment and uncertainty of modelling results. The results of this study indicate that these GASEMT database attributes had smaller impact on the number of citations, according to the BRT model, than anticipated, which could suggest that these attributes should be given additional attention by the soil erosion modelling community. This study provides a kind of bibliographic benchmark for soil erosion modelling research papers as modellers can estimate the influence of their paper.
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http://dx.doi.org/10.1016/j.envres.2021.111087DOI Listing
June 2021

Soil erosion modelling: A global review and statistical analysis.

Sci Total Environ 2021 Aug 17;780:146494. Epub 2021 Mar 17.

University of Twente, Faculty of Geo-Information Science and Earth Observation (ITC), PO Box 217, Enschede AE 7500, the Netherlands.

To gain a better understanding of the global application of soil erosion prediction models, we comprehensively reviewed relevant peer-reviewed research literature on soil-erosion modelling published between 1994 and 2017. We aimed to identify (i) the processes and models most frequently addressed in the literature, (ii) the regions within which models are primarily applied, (iii) the regions which remain unaddressed and why, and (iv) how frequently studies are conducted to validate/evaluate model outcomes relative to measured data. To perform this task, we combined the collective knowledge of 67 soil-erosion scientists from 25 countries. The resulting database, named 'Global Applications of Soil Erosion Modelling Tracker (GASEMT)', includes 3030 individual modelling records from 126 countries, encompassing all continents (except Antarctica). Out of the 8471 articles identified as potentially relevant, we reviewed 1697 appropriate articles and systematically evaluated and transferred 42 relevant attributes into the database. This GASEMT database provides comprehensive insights into the state-of-the-art of soil- erosion models and model applications worldwide. This database intends to support the upcoming country-based United Nations global soil-erosion assessment in addition to helping to inform soil erosion research priorities by building a foundation for future targeted, in-depth analyses. GASEMT is an open-source database available to the entire user-community to develop research, rectify errors, and make future expansions.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140410PMC
August 2021

The Neuroprotective Effect of Short Chain Fatty Acids Against Sepsis-Associated Encephalopathy in Mice.

Front Immunol 2021 28;12:626894. Epub 2021 Jan 28.

Department of Emergency Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Short chain fatty acids (SCFAs) are known to be actively involved in multiple brain disorders, but their roles in sepsis-associated encephalopathy (SAE) remain unclear. Here, we investigated the neuroprotective effects of SCFAs on SAE in mice. Male C57BL/6 mice were intragastrically pretreated with SCFAs for seven successive days, and then subjected to SAE induced by cecal ligation and puncture. The behavioral impairment, neuronal degeneration, and levels of inflammatory cytokines were assessed. The expressions of tight junction (TJ) proteins, including occludin and zoula occludens-1 (ZO-1), cyclooxygenase-2 (COX-2), cluster of differentiation 11b (CD11b), and phosphorylation of JNK and NF-κB p65 in the brain, were measured by western blot and Immunofluorescence analysis. Our results showed that SCFAs significantly attenuated behavioral impairment and neuronal degeneration, and decreased the levels of IL-1β and IL-6 in the brain of SAE mice. Additionally, SCFAs upregulated the expressions of occludin and ZO-1 and downregulated the expressions of COX-2, CD11b, and phosphorylation of JNK and NF-κB p65 in the brain of SAE mice. These findings suggested that SCFAs could exert neuroprotective effects against SAE in mice.
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http://dx.doi.org/10.3389/fimmu.2021.626894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876449PMC
January 2021

MCTR3 reduces LPS-induced acute lung injury in mice via the ALX/PINK1 signaling pathway.

Int Immunopharmacol 2021 Jan 29;90:107142. Epub 2020 Nov 29.

Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address:

Acute lung injury (ALI), a common respiratory distress syndrome in the intensive care unit (ICU), is mainly caused by severe infection and shock. Epithelial and capillary endothelial cell injury, interstitial edema and inflammatory cell infiltration are the main pathological changes observed in ALI animal models. Maresin conjugates in tissue regeneration (MCTR) are a new family of anti-inflammatory proteins. MCTR3 is a key enhancer of the host response, that promotes tissue regeneration and reduces infection; however, its role and mechanism in ALI are still unclear. The purpose of our research was to assess the protective effects of MCTR3 against ALI and its underlying mechanism. The work in this study was conducted in a murine model and the pulmonary epithelial cell line MLE-12. In vivo, MCTR3 (2 ng/g) was given 2 h after lipopolysaccharide (LPS) injection. We found that the treatment of mice with LPS-induced ALI with MCTR3 significantly reduced the cell number and protein levels in the bronchoalveolar lavage fluid (BALF); decreased the production of inflammatory cytokines; alleviated oxidative stress and cell apoptosis, consequently decreased lung injury; and restored pulmonary function. These protective effects of MCTR3 were dependent on down-regulation of the PTEN-induced putative kinase 1 (PINK1) pathway. Additionally, in MLE-12 cells stimulated with LPS, MCTR3 inhibited cell death, inflammatory cytokine levels and oxidative stress via the ALX/PINK1 signaling pathway. Thus, we conclude that MCTR3 protected against LPS-induced ALI partly through inactivation of the ALX/PINK1 mediated mitophagy pathway.
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http://dx.doi.org/10.1016/j.intimp.2020.107142DOI Listing
January 2021

Plasma ZO-1 proteins predict the severity and outcome of sepsis: A prospective observational study.

Clin Chim Acta 2020 Nov 8;510:691-696. Epub 2020 Sep 8.

Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, PR China. Electronic address:

Background: We determined whether plasma concentrations of ZO-1 proteins may be used a predictor of sepsis severity and 30-day mortality.

Methods: A total of 143 patients with sepsis and 30 healthy controls were enrolled. Plasma ZO-1 proteins concentrations were measured. Various methods, including area under the curves (AUCs), Kaplan-Meier curve, Cox regression, net reclassification improvement (NRI) and integrated discrimination improvement (IDI), were carried out to determine the value of ZO-1 in predicting 30-day mortality.

Results: Plasma ZO-1 concentrations in patients with sepsis and septic shock were significantly higher than those in healthy controls and were associated with the number of organ failures. ZO-1 concentrations also correlated with APACHE II or SOFA score and predicted 30-day mortality in sepsis patients with an AUC of 0.754. Multivariable regression analyses showed that a ZO-1 concentration ≥2.60 ng/ml remained a significant predictor of 30-day mortality in sepsis patients. Kaplan-Meier survival plots showed that patients with ZO-1 concentrations <2.60 ng/ml had a clear survival benefit. Adding ZO-1 to the SOFA score significantly improved its prognostic accuracy.

Conclusion: Plasma ZO-1 proteins appear to be a valuable prognostic biomarker for the severity of sepsis and a predictor of 30-day mortality for patients with sepsis.
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http://dx.doi.org/10.1016/j.cca.2020.09.003DOI Listing
November 2020

Gas6 attenuates lipopolysaccharide‑induced TNF‑α expression and apoptosis in H9C2 cells through NF‑κB and MAPK inhibition via the Axl/PI3K/Akt pathway.

Int J Mol Med 2019 Sep 12;44(3):982-994. Epub 2019 Jul 12.

Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.

Therapeutic agents used to treat sepsis‑induced cardiac dysfunction are designed to suppress tumor necrosis factor (TNF)‑α release and inhibit cell apoptosis. Exogenous administration of growth arrest‑specific 6 (Gas6) exerts several biological and pharmacological effects; however, the role of Gas6 in sepsis‑induced myocardial dysfunction remains unclear. In this study, H9C2 cardiomyocytes were stimulated with LPS (10 µg/ml) to mimic septic cardiac dysfunction and Gas6 (100 ng/ml) was applied exogenously. Subsequently, mitogen‑activated protein kinase (MAPK) and nuclear factor (NF)‑κB activation, TNF‑α expression, and apoptosis in the presence or absence of TP‑0903 (15 nM) and Wortmannin (3 nM) were evaluated. The morphological alterations of H9C2 cells were visualized by phase‑contrast microscopy. Cell viability was determined using the Cell Counting kit 8 assay and lactate dehydrogenase release, and TNF‑α release was analyzed by ELISA analysis. Cell apoptosis was analyzed by flow cytometry and TUNEL assay. Nuclear morphological alterations were detected by Hoechst staining and caspase‑3 activity was measured using biochemical methods. The expression levels of Bax and Bcl‑2, and the phosphorylation and expression levels of Axl, Akt, IκB‑α, p65, c‑Jun N‑terminal protein kinase (JNK), extracellular signal‑regulated kinase (ERK) and p38 were determined by western blotting. Furthermore, immunofluorescence analysis was performed to visualize translocation of NF‑κB p65. The results demonstrated that Gas6 suppressed TNF‑α release and inhibited cell apoptosis, and attenuated nuclear factor (NF)‑κB and mitogen‑activated protein kinase (MAPK) activation via the Axl/PI3K/Akt pathway. Furthermore, the cardioprotective properties of Gas6 on the suppression of LPS‑induced TNF‑α release and apoptosis were abolished by treatment with TP‑0903 (an Axl inhibitor) and Wortmannin (a PI3K inhibitor). Pretreatment with TP‑0903 and Wortmannin abrogated the effects of Gas6 on phosphorylated‑IκB‑α, IκB‑α, NF‑κB, ERK1/2, JNK and p38 MAPK. These findings suggested that activation of Axl/PI3K/Akt signaling by Gas6 may inhibit LPS‑induced TNF‑α expression and apoptosis, as well as MAPK and NF‑κB activation.
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http://dx.doi.org/10.3892/ijmm.2019.4275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657963PMC
September 2019

Hydrologic alteration and possible underlying causes in the Wuding River, China.

Sci Total Environ 2019 Nov 23;693:133556. Epub 2019 Jul 23.

State Key Laboratory of Soil Erosion and Dryland Farming on the Loess Plateau, Institute of Soil and Water Conservation, Northwest A&F University, Yangling, Shaanxi 712100, China; Institute of Soil and Water Conservation, Chinese Academy of Sciences & Ministry of Water Resources, Yangling, Shaanxi 712100, China.

Understanding hydrological alteration of rivers and the potential driving factors are crucial for water resources management in the watershed. This study analyzed the daily runoff time series at six gauging stations during 1960-2016 in Wuding River basin, northwestern China. The Mann-Kendall test and Lee-Heghinian method were employed to detect the temporal trends and abrupt changes in annual streamflow. The flow duration curve (FDC) and the index of hydrologic alteration (IHA)/Range of Variability Approach (RVA) were applied to assess the daily streamflow and degree of hydrologic alteration (DHA). In addition, we analyzed the changes of index of hydrological connectivity (IC) and reservoirs/dams (RI) in 1990, 1995, 2000 and 2015 in the basin. The relationship between IC, RI and DHA were assessed to investigate the potential influences of land use changes and constructions of reservoirs/dams on hydrological alteration. The results indicated that annual streamflow at five stations showed significant downward trends (p < 0.01) from 1960 to 2016, and an abrupt changing point appeared in the beginning of 1970s in Wuding River basin. Exception is Qingyangcha station without significant changes, and Hanjiamao station with changing point in 1967. FDC analysis indicated that both high and low flow indices reduced greatly. The integral DHA were higher than 70% at all the stations in the Wuding River basin, suggesting great variation in the magnitude, duration, frequency, timing and rate of change of daily streamflow. Both IC value and RI had close relationship with DHA, implying that DHA was highly affected by land use changes and dams/reservoirs constructions, and was more sensitive to the land use change (p < 0.01). This study provides good insight to understand the effects of soil and water conservation measures on hydrological regime.
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http://dx.doi.org/10.1016/j.scitotenv.2019.07.362DOI Listing
November 2019

Gas6 Attenuates Sepsis-Induced Tight Junction Injury and Vascular Endothelial Hyperpermeability the Axl/NF-κB Signaling Pathway.

Front Pharmacol 2019 13;10:662. Epub 2019 Jun 13.

Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Vascular endothelial functional dysregulation and barrier disruption are involved the initiation and development of sepsis. Growth arrest-specific protein 6 (Gas6), one of the endogenous ligands of TAM receptors (Tyro3, Axl, and Mertk), is confirmed to have beneficial functions in hemostasis, inflammation, and cancer growth. Here, we demonstrated the protective effects of Gas6 on multi-organ dysfunction syndrome (MODS) in sepsis and the underlying mechanisms. We investigated Gas6-ameliorated MODS by inhibiting vascular endothelial hyperpermeability in a mouse model of sepsis. Additionally, , under lipopolysaccharide (LPS) stimulation in vascular endothelial cells, Gas6 attenuated vascular endothelial hyperpermeability by reinforcing the tight junction proteins occludin, zonula occludens-1 (ZO-1), and claudin5. Furthermore, Gas6 substantially suppressed NF-κB p65 activation. In addition, blocking the Gas6 receptor, Axl, partially reduced the protective effect of Gas6 on the vascular endothelial barrier and diminished the inhibitive effect of Gas6 on NF-κB p65 activation. Taken together, this study suggests that Gas6 has a protective effect on MODS in sepsis by inhibiting the vascular endothelial hyperpermeability and alteration of tight junction and that the Axl/NF-κB signaling pathway underlies these effects.
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http://dx.doi.org/10.3389/fphar.2019.00662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585310PMC
June 2019

Reduced sediment transport in the Chinese Loess Plateau due to climate change and human activities.

Sci Total Environ 2018 Nov 14;642:591-600. Epub 2018 Jun 14.

State Key Laboratory of Soil Erosion and Dryland Farming on the Loess Plateau, Northwest A&F University, Yangling, China; Institute of Soil and Water Conservation, Chinese Academy of Sciences and Ministry of Water Resources, Yangling, China.

The sediment load on the Chinese Loess Plateau has sharply decreased in recent years. However, the contribution of terrace construction and vegetation restoration projects to sediment discharge reduction remains uncertain. In this paper, eight catchments located in the Loess Plateau were chosen to explore the effects of different driving factors on sediment discharge changes during the period from the 1960s to 2012. Attribution approaches were applied to evaluate the effects of climate, terrace, and vegetation coverage changes on sediment discharge. The results showed that the annual sediment discharge decreased significantly in all catchments ranging from -0.007 to -0.039 Gt·yr. Sediment discharge in most tributaries has shown abrupt changes since 1996, and the total sediment discharge was reduced by 60.1% during 1997-2012. We determined that increasing vegetation coverage was the primary factor driving the reductions in sediment loads since 1996 and accounted for 47.7% of the total reduction. Climate variability and terrace construction accounted for 9.1% and 18.6% of sediment discharge reductions, respectively.
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http://dx.doi.org/10.1016/j.scitotenv.2018.06.061DOI Listing
November 2018

Assessing response of sediment load variation to climate change and human activities with six different approaches.

Sci Total Environ 2018 Oct 26;639:773-784. Epub 2018 May 26.

Key Laboratory of Watershed Geographic Sciences, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing 210008, China.

Understanding the relative contributions of climate change and human activities to variations in sediment load is of great importance for regional soil, and river basin management. Considerable studies have investigated spatial-temporal variation of sediment load within the Loess Plateau; however, contradictory findings exist among methods used. This study systematically reviewed six quantitative methods: simple linear regression, double mass curve, sediment identity factor analysis, dam-sedimentation based method, the Sediment Delivery Distributed (SEDD) model, and the Soil Water Assessment Tool (SWAT) model. The calculation procedures and merits for each method were systematically explained. A case study in the Huangfuchuan watershed on the northern Loess Plateau has been undertaken. The results showed that sediment load had been reduced by 70.5% during the changing period from 1990 to 2012 compared to that of the baseline period from 1955 to 1989. Human activities accounted for an average of 93.6 ± 4.1% of the total decline in sediment load, whereas climate change contributed 6.4 ± 4.1%. Five methods produced similar estimates, but the linear regression yielded relatively different results. The results of this study provide a good reference for assessing the effects of climate change and human activities on sediment load variation by using different methods.
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http://dx.doi.org/10.1016/j.scitotenv.2018.05.154DOI Listing
October 2018

Curcumin attenuates sepsis-induced acute organ dysfunction by preventing inflammation and enhancing the suppressive function of Tregs.

Int Immunopharmacol 2018 Aug 17;61:1-7. Epub 2018 May 17.

Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Wenzhou Key Laboratory of Emergency, Critical care, and Disaster Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; College of Nursing, Wenzhou Medical University, Wenzhou 325000, China. Electronic address:

Sepsis is characterized by the extensive release of cytokines and other mediators. It results in a dysregulated immune response and can lead to organ damage and death. Curcumin has anti-inflammatory properties and immunoregulation functions in various disorders such as sepsis, cancer, rheumatoid arthritis, cardiovascular diseases, lung fibrosis, gallstone formation, and diabetes. This paper investigates the effects of curcumin on immune status and inflammatory response in mice subjected to cecal ligation and puncture (CLP). Inflammatory tissue injury was evaluated by histological observation. Magnetic microbeads were used to isolate splenic CD4CD25regulatory T cells (Tregs), and phenotypes were then analyzed by flow cytometry. The levels of Foxp3 were detected by Western blot and real-time PCR and cytokine levels were determined by enzyme-linked immunosorbent assay. We found that the administration of curcumin significantly alleviated inflammatory injury of the lung and kidney in septic mice. The suppressive function of Treg cells was enhanced and the plasma levels of IL-10 increased after treatment with curcumin. Furthermore, the secretion of plasma TNF-α and IL-6 was notably inhibited in septic mice treated with curcumin and administration with curcumin could improve survival after CLP. These data suggest that curcumin could be used as a potential therapeutic agent for sepsis.
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http://dx.doi.org/10.1016/j.intimp.2018.04.041DOI Listing
August 2018

Diagnostic value of complete blood count in paraquat and organophosphorus poisoning patients.

Toxicol Ind Health 2018 Jul 18;34(7):439-447. Epub 2018 Apr 18.

1 Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Complete blood count (CBC) is one of the most extensively used tests in clinical practice. In order to determine the diagnostic value of the CBC in paraquat (PQ) and organophosphorus (OPPs) poisoning, the CBC indices of PQ- and OPPs-poisoned patients were investigated in this study. A total of 96 PQ poisoning patients, 90 OPPs poisoning patients, and 188 healthy subjects were included in this study. The PQ- and OPPs-poisoned patients were divided into different groups according to their clinical symptoms. All CBC indices were analyzed by Fisher discriminant, partial least-squares discriminant analysis (PLS-DA), variance analysis, and receiver operating characteristic (ROC). The discriminant results showed that 87.7% of original grouped cases correctly classified between PQ-poisoned patients, OPPs-poisoned patients, and healthy subjects. The PLS-DA results showed that the important variable order was different in PQ- and OPPs-poisoned patients. Both white blood cell (WBC) and neutrophil (NE) counts were the most important indexes in PQ- and OPPs-poisoned patients. In OPPs poisoning patients, WBC and NE showed statistical differences between the severe poisoning group and the moderate poisoning group. Their areas under the ROC curve (AUC) were 0.673 (WBC) and 0.669 (NE), which were higher than cholinesterase (CHE; AUC 0.326). In conclusion, the CBC indices had a diagnostic value in PQ and OPPs poisoning; WBC and NE were the first responses and had clinical significance in PQ and OPPs poisoning; moreover, they are better than CHE in diagnosing OPPs poisoning.
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http://dx.doi.org/10.1177/0748233718770896DOI Listing
July 2018

Klotho ameliorates sepsis-induced acute kidney injury but is irrelevant to autophagy.

Onco Targets Ther 2018 19;11:867-881. Epub 2018 Feb 19.

Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Background: The role of Klotho (KL) in sepsis-induced acute kidney injury (AKI) and the potential relationship between KL and autophagy in septic AKI were investigated.

Materials And Methods: A murine model of sepsis-induced AKI was established by cecal ligation and puncture (CLP). Mice undergoing CLP and immortalized proximal tubular epithelial human HK-2 cells that were exposed to lipopolysaccharide (LPS) were treated with recombinant KL, autophagy stimulator rapamycin (Rap), and autophagy suppressor 3-methyladenine (3-MA).

Results: Autophagy activation and KL reduction reached maximum levels in mice 24 hours after CLP. Recombinant KL and/or Rap significantly attenuated CLP-induced renal dysfunction (<0.05) and partially restored endogenous renal KL expression (<0.05). Recombinant KL had no impact on CLP-induced autophagy and apoptosis, whereas Rap significantly stimulated autophagy and reduced apoptosis in mice. 3-MA significantly exacerbated renal dysfunction, increased apoptosis, and inhibited autophagy in mice with CLP-induced AKI (all <0.05). In LPS-treated HK-2 cells, Rap significantly enhanced autophagy and reduced apoptosis (all <0.05), whereas recombinant KL had no impact, and 3-MA inhibited autophagy and significantly increased apoptosis (<0.05).

Conclusion: Recombinant KL alleviates renal dysfunction and restores renal KL expression in mice with sepsis-induced AKI, but the underlying mechanism may not be related to autophagy induction.
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http://dx.doi.org/10.2147/OTT.S156891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823070PMC
February 2018

Comparison of prognostic, clinical, and renal histopathological characteristics of overlapping idiopathic membranous nephropathy and IgA nephropathy versus idiopathic membranous nephropathy.

Sci Rep 2017 09 13;7(1):11468. Epub 2017 Sep 13.

Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.

Overlapping idiopathic membranous nephropathy (IMN) and immunoglobulin A nephropathy (IgAN) is rare. This study aims to investigate the unique prognostic, clinical, and renal histopathological characteristics of IMN+IgAN. This retrospective observational study included 73 consecutive cases of IMN+IgAN and 425 cases of IMN treated between September 2006 and November 2015. Prognostic and baseline clinical and histopathological data were compared between the two patient groups. Poor prognostic events included a permanent 50% reduction in eGFR, end-stage renal disease, and all-cause mortality. Renal histopathology demonstrated that the patients with IMN+IgAN presented with significantly increased mesangial cell proliferation and matrix expansion, increased inflammatory cell infiltration, and higher proportions of arteriole hyalinosis and lesions than the patients with IMN (all P < 0.05). Kaplan-Meier analysis showed that the patients with IMN+IgAN had significantly higher cumulative incidence rates of partial or complete remission (PR or CR, P = 0.0085). Multivariate Cox model analysis revealed that old age at biopsy and high baseline serum creatinine and uric acid levels were significantly associated with poor prognosis (all P < 0.05), and increased IgA expression correlated significantly with PR or CR (P < 0.05). The present study found that overlapping IMN and IgAN presents with unique renal histopathology and appears not to cause a poorer prognosis than IMN.
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http://dx.doi.org/10.1038/s41598-017-11838-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597578PMC
September 2017

Crosstalk between Mitochondrial Fission and Oxidative Stress in Paraquat-Induced Apoptosis in Mouse Alveolar Type II Cells.

Int J Biol Sci 2017 7;13(7):888-900. Epub 2017 Jul 7.

Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.

Paraquat (PQ), as a highly effective and nonselective herbicide, induces cell apoptosis through generation of superoxide anions which forms reactive oxygen species (ROS). Mitochondria, as regulators for cellular redox signaling, have been proved to play an important role in PQ-induced cell apoptosis. This study aimed to evaluate whether and how mitochondrial fission interacts with oxidative stress in PQ-induced apoptosis in mouse alveolar type II (AT-II) cells. Firstly, we demonstrated that PQ promoted apoptosis and release of cytochrome-c (Cyt-c). Furthermore, we showed that PQ broke down mitochondrial network, enhanced the expression of fission-related proteins, increased Drp1 mitochondrial translocation while decreased the expression of fusion-related proteins in AT-II cells. Besides, inhibiting mitochondrial fission using mdivi-1, a selective inhibitor of Drp1, markedly attenuated PQ-induced apoptosis, release of Cyt-c and the generation of ROS. These results indicate that mitochondrial fission involves in PQ-induced apoptosis. Further study demonstrated that antioxidant ascorbic acid inhibited Drp1 mitochondrial translocation, mitochondrial fission and attenuated PQ-induced apoptosis. Overall, our findings suggest that mitochondrial fission interplays with ROS in PQ-induced apoptosis in mouse AT-II cells and mitochondrial fission could serve as a potential therapeutic target in PQ poisoning.
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http://dx.doi.org/10.7150/ijbs.18468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555106PMC
May 2018

Effects of hemoperfusion and continuous renal replacement therapy on patient survival following paraquat poisoning.

PLoS One 2017 13;12(7):e0181207. Epub 2017 Jul 13.

Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Mortality in patients with paraquat (PQ) poisoning is related to plasma PQ levels. Concentrations lower than 5,000 ng/mL are considered critical but curable. This study assessed the effects of hemoperfusion (HP) and continuous renal replacement therapy (CRRT) on the survival of PQ-poisoned patients with plasma PQ levels below 5,000ng/mL. We analyzed the records of 164 patients with PQ poisoning who were treated at the First Affiliated Hospital of Wenzhou Medical University in China between January 2011 and May 2015. We divided these patients into six sub-groups based on baseline plasma PQ levels and treatment, compared their clinical characteristics, and analyzed their survival rates. Patient sub-groups did not differ in terms of age, sex, time between poisoning and hospital admission, or time to first gavage. Biochemical indicators improved over time in all sub-groups following treatment, and the combined HP and CRRT treatment yielded better results than HP or CRRT alone. Fatality rates in the three treatment sub-groups did not differ among patients with baseline plasma PQ levels of 50-1,000 ng/mL, but in patients with 1,000-5,000 ng/mL levels, the mortality rate was 59.2% (HP treatment group), 48% (CRRT treatment group), and 37.9% (combined treatment group). Mortality rates were higher 10-30 days after hospitalization than in the first 10 days after admission. In the early stages of PQ poisoning, CRRT is effective in reducing patient fatality rates, particularly when combined with HP. Our data could be useful in increasing survival in acute PQ poisoning patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181207PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509301PMC
September 2017

Dynamic sediment discharge in the Hekou-Longmen region of Yellow River and soil and water conservation implications.

Sci Total Environ 2017 Feb 7;578:56-66. Epub 2016 Jul 7.

Institute of Soil and Water Conservation, Northwest A&F University, Yangling, Shaanxi Province 712100, China.

The middle reaches of the Yellow River Basin transport the vast majority of sediment (>85% of the basin's total available sediment load), which has had profound effects on the characteristics of the middle and lower reaches of the Yellow River. Since the late 1950s, soil and water conservation measures have been extensively implemented in the Loess Plateau, China, especially since the 1970s. This has resulted in sediment discharge changing significantly. In this study, data from 22 catchments in the region of the Loess Plateau from Hekou to Longmen in the middle reaches of the Yellow River were analyzed to investigate the responses of the sediment regime to climate change and human activities. The non-parametric Mann-Kendall test and the Pettitt test were used to identify trends and shifts in sediment discharge. All 22 catchments had a significantly decreasing trend (P<0.01) in annual sediment discharge. Change point years were detected between 1971 and 1994, and were concentrated between 1978 and 1984 in 17 catchments. Moreover, erosive rainfall exhibited a tendency to decrease, but this was not a significant trend. Compared to rainfall, human activities, primarily soil and water conservation and environmental rehabilitation campaigns, have played a more prominent role in the changes in sediment regimes. In order to reduce soil erosion and sediment yield, more attention should be paid to proper and rational soil and water conservation and eco-restoration in this region.
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http://dx.doi.org/10.1016/j.scitotenv.2016.06.128DOI Listing
February 2017

Prognosis and survival analysis of paraquat poisoned patients based on improved HPLC-UV method.

J Pharmacol Toxicol Methods 2016 Jul-Aug;80:75-81. Epub 2016 May 20.

Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address:

Unlabelled: Paraquat (PQ) has caused deaths of numerous people around the world. In order to assess the lethal plasma concentration, the patients who acquired acute PQ intoxication were analyzed by plasma concentration monitoring. The plasma PQ concentrations were determined by high performance liquid chromatography (HPLC) which used 5-bromopyrimidine as internal standard and trichloroacetic acid-methanol (1:9) as protein precipitant. The liver, kidney and coagulation function were determined by automatic biochemical analyzer. According to plasma PQ concentration, 90 patients were divided into four groups: trace PQ group (<50ng/mL), low PQ group (<1000ng/mL), medium PQ group (1000-5000ng/mL) and high PQ group (>5000ng/mL). The clinical data from the four groups was statistically analyzed. The results showed the developed HPLC methods exhibited a high degree of accuracy and good linearity within 50-25000ng/mL (R=0.9998). The Spearman's correlation analysis showed PQ concentration had a strong relationship to total bilirubin, direct bilirubin, aspartic transaminase, urea nitrogen, prothrombin time, prothrombin activity, and international normalized ratio (P<0.01). The cured or survival PQ poisoned patients among the trace PQ group, the low PQ group, the medium PQ group, and the high PQ group were 19/19 (100%), 19/21 (90.47%), 11/25 (44.0%), and 0/25 (0%) respectively. The mean hospital days were (10.37±8.04), (18.76±12.06), (16.76±14.44), and (4.04±5.41) days respectively. The Cox regression analysis indicated that plasma PQ concentration was highly related to prognosis (P<0.05). In conclusion, no patient presenting with a PQ concentration over 5000ng/mL survived. The plasma PQ level is related to liver, kidney and coagulation function, which can be used as an important clinical index to judge the prognosis of PQ poisoned patients.

Chemical Compounds: Paraquat (PubChem CID: 15938), 5-bromopyrimidine (PubChem CID: 78344), acetonitrile (PubChem CID: 6342), sodium dihydrogen phosphate (PubChem CID: 23672064), sodium heptanesulfonate (PubChem CID: 23672332), methylprednisolone (PubChem CID: 6741), cyclophosphamide (PubChem CID: 2907).
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http://dx.doi.org/10.1016/j.vascn.2016.05.010DOI Listing
May 2017

[The protective effect of bone marrow mesenchymal stem cells carrying antioxidant gene superoxide dismutase on paraquat lung injury in mice].

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2016 Jan;34(1):1-7

Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.

Objective: To explore the possible mechanism and protective effect of BMSCs (bone mesenchymal stem cells) carrying superoxide dismutase (SOD) gene on mice with paraquat-induced acute lung injury.

Methods: To establish the cell line of BMSCs bringing SOD gene, lentiviral vector bringing SOD gene was built and co-cultured with BMSCs. A total of 100 BALB/c mice were randomly divided into five groups, namely Control group, poisoning group (PQ group) , BMSCs therapy group (BMSC group) , BMSCs-Cherry therapy group (BMSC-Cherry group) , BMSCs-SOD therapy group (BMSC-SOD group) . PQ poisoning model was produced by stomach lavaged once with 1 ml of 25 mg/kg PQ solution, and the equal volume of normal saline (NS) was given to Control group mice instead of PQ. The corresponding BMSCs therapy cell lines were delivered to mice through the tail vein of mice 4h after PQ treatment.Five mice of each group were sacrificed 3 d, 7 d, 14 d and 21 days after corresponding BMSCs therapy cell lines administration, and lung tissues of mice were taken to make sections for histological analysis. The serum levels of glutathione (GSH) , malondialdehyde (MDA) , SOD, and the levels of transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) in lung tissue were determined. The level of SOD was assayed by Westen-blot.

Results: Compared with Control group, the early (3 days) levels of SOD protein in lung tissue of PQ group obviously decreased, and the late (21 days) levels of SOD obviously increased, while in therapy groups, that was higher than that in PQ group, and the BMSCs-SOD group showed most obvious (all P<0.05) . Compared with Control group, the levels of plasma GSH and SOD of PQ group and each therapy group wae significantly lower than those in Control group, while in therapy groups, those were higher than those of PQ group, and the BMSCs-SOD group showed most obvious (all P<0.05) .Compared with Control group, the level of plasma MDA, TNF-α and TGF-β in PQ group and therapy groups were significantly higher, while in therapy groups, that was lower than that in PQ group, and the BMSCs-SOD group showed most obvious (all P<0.05) . Lung biopsy showed that, the degree of lung tissue damage in each therapy group obviously reduced.

Conclusion: SOD is the key factor of the removal of reactive oxygen species (ROS) in cells, that can obviously inhibit the oxidative stress damage and the apoptosis induced by PQ, thus significantly increasing alveolar epithelial cell ability to fight outside harmful environment.
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http://dx.doi.org/10.3760/cma.j.issn.1001-9391.2016.01.001DOI Listing
January 2016

[Effect of PON1 overexpression on mouse diaphragmatic muscle cells injury caused by acute dichlorvos poisoning].

Zhonghua Yi Xue Za Zhi 2015 Sep;95(36):2955-9

Wenzhou Medical University, Wenzhou 325000, China; Email:

Objective: To investigate the effect of paraoxonase1 (PON1) overexpression on mouse diaphragmatic muscle cells injury caused by acute dichlorvos poisoning.

Methods: Mouse diaphragmatic muscle cells were cultured routinely and infected with overexpression lentivirus. Cells were divided into normal control group, DDVP group, LV-GFP + DDVP group, LV-PON1 + DDVP group. Cell viability was determined by CCK-8 assay. Flow cytometry was used to detect cell apoptosis. The mRNA and protein expression of PON1 and Nrf2 in mouse diaphragmatic muscle cells was measured by RT-PCR and Western blot. Enzyme-linked immunosorbent assay was used to determine levels of acetyl cholinesterase (AchE), heme oxygenase 1 (HO-1) and quinone oxidoreductase-1 (NQO-1) in mouse diaphragmatic muscle cells. The activity of superoxide dismutase (SOD) and catalase (CAT) as well as malondialdehyde (MDA) content in cells was measured by chemical colorimetry.

Results: After induced by 0, 80, 160, 320, 640 µmol/L DDVP for 24 hours, the viability of mouse diaphragmatic muscle cells was (100 ± 3.82)%, (82.13 ± 2.60)%, (53.57 ± 5.05)%, (30.77 ± 3.30)%, (14.20 ± 2.19)% respectively, changing in a concentration-dependent manner (P < 0.05). After induced by 160 µmol/L DDVP for 0, 6, 12, 24 hours, the viability of mouse diaphragmatic muscle cells was (100.17 ± 2.74)%, (76.13 ± 6.01)%, (66.53 ± 3.55)%, (53.57 ± 5.05)%, changing in a time-dependent manner (P < 0.05). The PON1 protein level in LV-PON1 group was higher than that of blank control group (0.370 ± 0.015 vs 0.232 ± 0.004, 0.197 ± 0.015 vs 0.037 ± 0.003, P < 0.05). The cell viability of LV-PON1 group is higher than that of DDVP group at different time point after induction of DDVP (P < 0.05). After induced by DDVP for 24 hours, the cell apoptosis rate and MDA content in LV-PON1 group were lower than those of DDVP group (P < 0.05). While levels of AchE, PON1 and Nrf2 protein expression, SOD and CAT, HO-1 and NQO-1 were higher than those of DDVP group (P < 0.05).

Conclusions: The overexpression of PON1 could effectively alleviate AchE inhibition by DDVP and induce Nrf2 expression to exert antioxidant effect, thus protected the mouse diaphragmatic muscle cells.
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September 2015

[The effect of resveratrol on paraquat-induced acute lung injury in mice and its mechanism].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2016 Jan;28(1):33-7

Department of Emergency, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China. Corresponding author: Lu Zhongqiu, Email:

Objective: To investigate the effect of resveratrol (Res) on paraquat (PQ)-induced acute lung injury (ALI) and mortality in mice and the mechanism of nuclear factor-ΚB (NF-ΚB) inflammatory pathway.

Methods: Sixty-eight healthy male ICR mice with grade SPF were enrolled, among them 20 mice were used for mortality observation (n = 10), and other 48 were used for determination of related parameters (n = 6). The mice were randomly divided into four groups: normal saline (NS) control group, Res control group, PQ group and PQ + Res group. The mice in the latter two groups were subdivided into 6, 24, 72 hours subgroups. The PQ poisoning model of mice was reproduced by one injection of 30 mg/kg PQ intraperitoneally. The mice in PQ + Res group were given 60 mg/kg Res intraperitoneally on the contralateral side after PQ injection. The mice were sacrificed at 6, 24, 72 hours after PQ poisoning, and lung tissue was harvested. The serum levels of tumor necrosis factor-α (TNF-α), interleukins (IL-6 and IL-1β) were determined by enzyme linked immunosorbent assay (ELISA). The pathological changes in lung tissue were observed with electron microscopy. Apoptosis cells in the lung were identified by terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) for the estimation of apoptosis rate. The protein expression of NF-ΚB p65 was determined by Western Blot.

Results: Compared with PQ group, the death number of mice at 48, 72, 96 hours in PQ + Res group was slightly decreased (0 vs. 2, 2 vs. 5, 4 vs. 6) but without statistically significant difference (all P > 0.05). Under electron microscope, the lung injury in PQ group was severer than that in NS control group, and Res was found to be able to alleviate the lung injury. Compared with NS control group [(2.45±0.61)%], the apoptosis rate at 6 hours in PQ group was significantly increased [(8.42±1.48)%], and peaked at 72 hours [(21.23±3.47)%]. Res could decrease the apoptosis rate after PQ poisoning [6 hours: (5.56±1.31)% vs. (8.42±1.48)%, 24 hours: (11.14±2.07)% vs. (16.88±2.96)%, 72 hours: (13.28±2.32)% vs. (21.23±3.47)%, all P < 0.05]. The serum levels of TNF-α, IL-6, and IL-1β, and NF-ΚB p65 in lung tissue were all markedly increased after PQ poisoning, and they were significantly decreased after Res intervention as compared with those of PQ group [TNF-α (ng/L): 2.62±0.29 vs. 4.06±0.74 at 6 hours, 3.98±0.41 vs. 6.79±0.80 at 24 hours, 5.06±0.75 vs. 11.00±0.75 at 72 hours; IL-6 (ng/L): 14.19±1.54 vs. 16.55±1.24 at 6 hours, 13.21±1.37 vs. 19.73±0.85 at 24 hours, 13.72±0.56 vs. 22.45±0.72 at 72 hours; IL-1β (ng/L): 8.54±1.64 vs. 12.59±0.66 at 6 hours, 10.15±0.29 vs. 16.24±1.03 at 24 hours, 16.14±0.70 vs. 19.55±0.56 at 72 hours; 6-hour NF-ΚB p65: (1.34±0.07) folds vs. (1.86±0.11) folds when the expression in NS control group was represented as 1, all P < 0.05].

Conclusions: Res cannot lower the mortality in mice with PQ poisoning, but it seems to be able to attenuate PQ-induced ALI and cell apoptosis. The mechanism responsible for the latter maybe the inhibitive effect of Res on NF-ΚB p65 translocation and cytokines production.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2016.01.007DOI Listing
January 2016

Resveratrol protects mice from paraquat-induced lung injury: The important role of SIRT1 and NRF2 antioxidant pathways.

Mol Med Rep 2016 Feb 23;13(2):1833-8. Epub 2015 Dec 23.

Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.

Sirtuin 1 (SIRT1) acts via the deacetylation of a number of crucial transcription factors and has been implicated in various biological processes, including oxidative stress. Previous studies have indicated that nuclear factor, erythroid 2‑like 2 (NRF2) is an effective target of antioxidant therapy for paraquat (PQ) poisoning. However, the association between SIRT1 and NRF2 and their effects in PQ‑induced oxidative stress remains to be elucidated. The current study demonstrated that PQ exposure upregulated the expression of SIRT1 and NRF2 following 6‑ and 24‑h exposure in the lungs of mice. However, long‑term exposure to PQ significantly decreased the expression of SIRT1 and NRF2. Resveratrol is a SIRT1 activator, and strongly enhanced SIRT1 expression and attenuated the lung injury resulting from PQ exposure in the current study. Additionally, treatment with resveratrol upregulated the expression of NRF2 and glutathione, increased the activity of heme oxygenase‑1, superoxide dismutase and catalase, but depleted the expression of malondialdehyde. The present results demonstrated that resveratrol reduced PQ‑induced oxidative stress and lung injury, potentially through the positive feedback signaling loop between SIRT1 and NRF2.
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http://dx.doi.org/10.3892/mmr.2015.4710DOI Listing
February 2016

[The protective effect of ulinastatin on paraquat-induced injury in HK-2 cells and the underlying mechanisms].

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2015 Jul;33(7):501-6

Emergency Department of the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; E-mial:

Objective: To investigate the protective effect of ulinastatin (UTI) on HK-2 cells during paraquat (PQ)-induced injury and its underlying mechanisms.

Methods: Routinely cultured HK-2 cells were divided into blank control group, PQ group, UTI+PQ group and UTI group. Cell viability was determined by CCK-8 assay. The concentration of PQ in HK-2 cells were measured by high performance liquid chromatography (HPLC). The production of total reactive oxygen species (ROS) were detected by fluorescence microscopy. The activities of superoxide dismutase activity (SOD) and the content of malondialdehyde (MDA) in HK-2 cells were observed by chemical colorimetry. The levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA).

Results: PQ, even at a dose of 200 µM, could significant suppress the viability of HK-2 cells in a dose-dependent and time-dependent. UTI showed no significant inhibitory effect on the viability of HK-2 cells when given at a dose below 8 000 U/ml (P > 0.05). Compared with the PQ group, the UTI+PQ group had significantly increased the viability of HK-2 cells in a dose-dependent of UTI (P < 0.05). Compared with the PQ group on the same hour, the UTI+PQ group showed decreased in PQ concentration in HK-2 cells (P < 0.05 for all except 6 h). Compared with the blank control group, the PQ group had significantly decreased SOD activity and significantly increased ROS level and MDA content (P < 0.05). Compared with the PQ group, the UTI+PQ group had significantly increased SOD activity and significantly decreased ROS level and MDA content (P < 0.05). Compared with the blank control group, the PQ group had significantly increased IL-6 and TNF-α level (P < 0.05); Compared with the PQ group, the UTI+PQ group had significantly decreased IL-6 and TNF-α level (P < 0.05).

Conclusion: UTI significantly reduces the PQ-induced oxidative damage and inflammatory injury and its mechanism may be by reducing the accumulation of PQ in HK-2 cells.
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July 2015

Migration of a Metallic Foreign Body Into the Heart.

J Card Surg 2015 Dec 20;30(12):891-3. Epub 2015 Oct 20.

Department of Emergency Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

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http://dx.doi.org/10.1111/jocs.12648DOI Listing
December 2015

[Analyses on relevant factors of the prognosis of patients with acute organophosphate poisoning].

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2015 Mar;33(3):186-9

E-mail:

Objective: To find out a method which can assess the prognosis of patients with Acute Organophosphate Poisoning objectively and increase the successful ratio of treatment by investigating relevant factors on the prognosis of the patients with Acute Organophosphate Poisoning.

Methods: We retrospected 116 patients with Acute Organophosphate Poisoning who were treated in our hospital's emergency room from April 2006 to March 2014. According to the outcome of patients, we distributed the patients to death group and survival group, compared the clinic data and using multivariate analysis with Logistic regression to prognosis factors.

Results: 116 cases of acute organophosphate poisoning patients died in 23 cases, improved in 93 cases. Death group patients' APACHE-II score are higher than whose in the survival group (P < 0.05). Compared with the survival group, patients' body temperature, blood pressure, pH, GCS index were lower in the death group (P < 0.05) and Cr, WBC, ALT, AST, CK-MB, blood glucose, blood lactic acid, heart rate were higher in the death group (P < 0.05), there were significant difference between two groups with statistical.Low blood pressure, lower GCS score, hyperglycemia and high white blood cell count, were independent risk factors of poor prognosis, and hypotension was maximum value of all the factor (OR = 54.22).

Conclusion: APACHE II prognostic scoring system can be accurately response, vital signs, white blood cell count, pH, serum creatinine, GCS score and serum sodium value which in this system may be associated with prognosis. To evaluate the severity and prognosis of illness Blood glucose, ALT, AST, CK-MB's rising also has certain value.
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March 2015

[Effect of thalidomide in a mouse model of paraquat-induced acute lung injury and the underlying mechanisms].

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2014 Nov;32(11):806-12

Emergency Department of the First Affiliated Hospital of Wenzhou Medical university , Wenzhou 325000, China. E-mial:

Objective: To investigate the effects of thalidomide in a mouse model of paraquat-induced acute lung injury and the mechanisms underlying the properties of thalidomide.

Methods: Male ICR mice were randomly allocated into four groups: nomal control group (n = 30), thalidomide control group (n = 30), paraquat poisioning group (n = 30) and thalidomide treatment group (n = 90). Mice were sacrificed at 1d, 3d and 7d after paraquat poisioning. The level of (MDA) malondialdehyde, Superoxidedi-smutase (SOD) and glutathione (GSH) in the lung tissue were measuerd by chemical colorimetry. The expression of Nrf2 mRNA was determined by RT-PCR; Nuclear protein Nrf2 was abserved by Western blotting; Pathological changes of lung tissue were observed under light microscope by HE stain; the lung apoptosis cells were detected by TUNEL.

Results: The levels of MDA, SOD and the expressions Nrf2 mRNA and protein Nrf2 in lung tissue were all markedly increased in mice of paraquat poisioning group than those in nomal group at 1 d, 3 d, 7 d. In contrast, the levels of GSH were decreaseel (P<0.05). Compared with paraquat poisioning group, the pulmonary SOD, Nrf2 mRNA and protein were increased and the lung wet dry ratio were all significantly decreased in mice of THD treatment group at 1 d, 3 d, 7 d (P<0.05). THD alleviated the pulmonary damage in the lightmicroscope at 3d after paraquat poisioning. The apoptosis index was markedly decreased in THD treatment groups comparing to paraquat piosioning group (P<0.05).

Conclusions: Lipid peroxide damage was one of the mechanisms of paraquat poisioning, thalidomide could attenuate paraquat-induced acute lung injury and its mechanism may be activating the Nrf2-ARE signaling pathway to protect mouse from Lipid peroxide damage.
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November 2014

[The protective effect of bone marrow mesenchymal stem cell on lung injury induced by vibrio vulnificus sepsis].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2014 Nov;26(11):821-6

Department of Emergency, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, Zhejiang, China, Corresponding author: Lu Zhongqiu, Email:

Objective: To discuss the protective effect of bone marrow mesenchymal stem cell (BMSC) on lung injury induced by vibrio vulnificus sepsis and its mechanism.

Methods: BMSCs were isolated by whole bone marrow adherent culture from mouse. Male ICR mice were randomly divided into normal saline control group (NS group), normal saline + BMSC control group (NSB group), vibrio vulnificus sepsis group (VV group), vibrio vulnificus sepsis + BMSC group (VVB group) according to random number table, with 40 mice in each group. Sepsis mouse model was reproduced by injecting vibrio vulnificus (1 × 10⁷ cfu/mL) 5 mL/kg through the left side peritoneal cavity, and caudal intravenous injection of BMSC (4 × 10⁵ cfu/mL) 5 mL/kg for intervention after model reproduction. Ten mice in each group were sacrificed at 6, 12, 24 or 48 hours after injecting vibiro vulnificus, and their lung tissues were harvested. The lung wet/dry (W/D) ratio was calculated. The expression of nuclear factor-ΚBp65 (NF-ΚBp65) in nucleus was measured by Western Blot. The levels of tumor necrosis factor-α (TNF-α) and interleukins (IL-1β, IL-6) in lung tissue were detected by enzyme-linked immunosorbent assay (ELISA). The pathological changes in lung tissue were observed after hematoxylin-eosin (HE) staining and uranyl acetate-lead citrate staining.

Results: After vibrio vulnificus injection, lung W/D ratio, the expression of NF-ΚBp65 in nucleus, and the levels of TNF-α, IL-1β, IL-6 in the lung tissues were significantly increased in VV group compared with those in NS group at all the time points, and peaked at 12 hours. Compared with the VV group, the VVB group had significantly decreased levels of lung W/D ratio, NF-ΚBp65 expression, and the levels of TNF-α, IL-1β, IL-6, with significant differences at all the time points [VV group vs. NS group at 12 hours: lung W/D ratio 7.22 ± 0.03 vs. 5.21 ± 0.02, NF-ΚBp65 expression (glay scale) 1.86 ± 0.74 vs. 0.75 ± 0.07, TNF-α (ng/L) 433.24 ± 3.23 vs. 106.57 ± 1.21, IL-1β (ng/L) 35.64 ± 0.15 vs. 10.64 ± 0.48, IL-6 (ng/L) 58.84 ± 0.55 vs. 17.69 ± 1.35, all P<0.05; VVB group vs. VV group at 12 hours: lung W/D ratio 6.49 ± 0.06 vs. 7.22 ± 0.03, NF-ΚBp65 expression (A value) 1.16 ± 0.08 vs. 1.86 ± 0.74, TNF-α (ng/L) 357.22 ± 3.25 vs. 433.24 ± 3.23, IL-1β (ng/L) 27.77 ± 0.59 vs. 35.64 ± 0.15, IL-6 (ng/L) 38.6 8 ± 1.29 vs. 58.84 ± 0.55, all P<0.05]. There were no significant differences in above indexes between NS group and NSB group. In the NS and NSB groups pathological changes were not obvious under light microscopy, in the VV group lung tissue hyperemia and edema was significant, the edema fluid, red blood cells and inflammatory cells also could be seen, and in the VVB group lung damage that mentioned above could be alleviated. In the NS and NSB groups epithelial cell structure of type I and type II was completed, and the changes were not obvious under the transmission electron microscopy. In the VV group the alveolar walls were damaged significantly, with type I epithelial cell cytoplasm swelling, bubbling and rupture, with type II epithelial cells visible cytoplasm decrease, cavitation, addiction to osmium lamellar corpuscle emptying, lysosome hyperplasia, microvilli reduction, and in the VVB group the above damage was alleviated.

Conclusions: Vibrio vulnificus sepsis can cause acute lung damage and edema, and BMSC can down regulate inflammatory cytokines, reduce lung injury caused by vibrio vulnificus sepsis.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2014.11.011DOI Listing
November 2014

[An association between NF-E2-related factor 2-617 C/A gene polymorphisms and sepsis in Chinese Han population].

Zhonghua Nei Ke Za Zhi 2014 Jun;53(6):442-5

Emergency Medical Department, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou 325000, China. Email:

Objective: To investigate the association between the single nucleotide polymorphisms (SNPs) in NF-E2-related factor 2-617 (NRF2-617) promoter region with the susceptibility to the risk of sepsis.

Methods: In this case-control association study, 203 healthy controls and 174 patients with sepsis in Wenzhou Han population were enrolled and genotyped by DNA direct sequencing.

Results: (1) The (CA+AA) genotype frequency was significantly higher in the sepsis group than in the control group (59.2% vs 46.3%, P = 0.012). (2) Compared with the general sepsis group, higher (CA+AA) genotype frequency was found in the severe sepsis group (47.5% vs 65.5%, P = 0.033) . However, no significant difference was shown in the (CA+AA) genotype frequency between the shock group and the non-shock group as well as between the death group and the non-death group (61.8% vs 57.1%, P = 0.221; 56.8% vs 66.7%, P = 0.258) . (3) The unconditional logistic regression analysis showed that the mutation of C to A at the gene promoter locus of Nrf2-617 was associated with the increased onset risk of sepsis (OR = 1.584, 95%CI 1.025-2.447, P = 0.038) and the severity of sepsis (OR = 0.453, 95%CI 0.233-0.878, P = 0.019).

Conclusion: The mutation of C to A at the gene promoter locus of Nrf2-617 may increase the onset risk of sepsis and organ failure in sepsis patients, while not associated with the incidence of shock and the prognosis of sepsis.
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June 2014
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