Effect of Total Flavone of Haw Leaves on Nuclear Factor Erythroid-2 Related Factor and Other Related Factors in Nonalcoholic Steatohepatitis Rats
Objective To investigate the effect of total flavone of haw leaves (TFHL) on the expression of nuclear factor erythroid-2 related factor (Nrf2) and other related factors in nonalcoholic steatohepatitis (NASH) rats induced by high-fat diet and then to further discuss the mechanism of TFHL’s preventio...
Gespeichert in:
Veröffentlicht in: | Chinese journal of integrative medicine 2018-04, Vol.24 (4), p.265-271 |
---|---|
Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 271 |
---|---|
container_issue | 4 |
container_start_page | 265 |
container_title | Chinese journal of integrative medicine |
container_volume | 24 |
creator | Wang, De-jun Cai, Yue-qin Pan, Shui-zhen Zhang, Li-zong Chen, Yun-xiang Chen, Fang-ming Jin, Ming Yan, Mao-xiang Li, Xiao-dong Chen, Zhi-yun |
description | Objective
To investigate the effect of total flavone of haw leaves (TFHL) on the expression of nuclear factor erythroid-2 related factor (Nrf2) and other related factors in nonalcoholic steatohepatitis (NASH) rats induced by high-fat diet and then to further discuss the mechanism of TFHL’s prevention against NASH.
Methods
High-fat diet was fed to 40 rats to establish the NASH model. Then model rats were intragastrically administrated with 40, 80, 160 mg/(kg•day) TFHL, respectively. The pathological changes of liver tissues in NASH rats were detected by oil red O and hematoxylin-eosin (HE) stainings. The expression of Nrf2 in rat liver was examined through immunohistochemistry. The level of 8-iso-prostaglandin F2α in serum was detected through enzyme linked immunosorbent assay (ELISA). The mRNA and protein levels of Nrf2 and other related factors in liver tissue were measured by real-time reverse transcriptionpolymerase chain reaction and western blot.
Results
Lipid deposition, hepatic steatosis, focal necrosis in lobular inflammation and ballooning degeneration were emerged in livers of NASH rats. The 8-iso-prostaglandin F2α in the serum of NASH rats increased significantly compared with the control group (
P |
doi_str_mv | 10.1007/s11655-016-2450-0 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1826658081</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1826658081</sourcerecordid><originalsourceid>FETCH-LOGICAL-c344t-83b0030be1b0dbf529187e0f35a064d16d214063f7098d97cc51f25e87f6a1253</originalsourceid><addsrcrecordid>eNp9UU1v1DAQtRBVW0p_ABfkI5fAjBM7yRFVuxRpRaW2nC3HGbOpvPFiO0X9GfxjvNqWAwdO8zTv4_AeY-8QPiJA-ykhKikrQFWJRkIFr9g59n1dQQPidcGqFQWjPGNvUnoAkK0CecrOhOqx7-rmnP1eOUc28-D4fcjG87U3j2Gmw-Pa_OIbMo-UeJj5t8V6MpGvjc0h8lV8ytsYprES_Ja8yTS-UGYe-U3eUvyHSHwqMWE23oZt8JPld5lMDlvamzzlKfFbk9NbduKMT3T5fC_Y9_Xq_uq62tx8-Xr1eVPZumly1dUDQA0D4QDj4KTosWsJXC0NqGZENQpsQNWuhb4b-9ZaiU5I6lqnDApZX7APx9x9DD8XSlnvpmTJezNTWJLGTiglO-iwSPEotTGkFMnpfZx2Jj5pBH1YQh-X0GUJfVhCQ_G8f45fhh2Nfx0v1ReBOApSoeYfFPVDWGIpJ_0n9Q-255Oi</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1826658081</pqid></control><display><type>article</type><title>Effect of Total Flavone of Haw Leaves on Nuclear Factor Erythroid-2 Related Factor and Other Related Factors in Nonalcoholic Steatohepatitis Rats</title><source>MEDLINE</source><source>SpringerLink Journals</source><source>Alma/SFX Local Collection</source><creator>Wang, De-jun ; Cai, Yue-qin ; Pan, Shui-zhen ; Zhang, Li-zong ; Chen, Yun-xiang ; Chen, Fang-ming ; Jin, Ming ; Yan, Mao-xiang ; Li, Xiao-dong ; Chen, Zhi-yun</creator><creatorcontrib>Wang, De-jun ; Cai, Yue-qin ; Pan, Shui-zhen ; Zhang, Li-zong ; Chen, Yun-xiang ; Chen, Fang-ming ; Jin, Ming ; Yan, Mao-xiang ; Li, Xiao-dong ; Chen, Zhi-yun</creatorcontrib><description>Objective
To investigate the effect of total flavone of haw leaves (TFHL) on the expression of nuclear factor erythroid-2 related factor (Nrf2) and other related factors in nonalcoholic steatohepatitis (NASH) rats induced by high-fat diet and then to further discuss the mechanism of TFHL’s prevention against NASH.
Methods
High-fat diet was fed to 40 rats to establish the NASH model. Then model rats were intragastrically administrated with 40, 80, 160 mg/(kg•day) TFHL, respectively. The pathological changes of liver tissues in NASH rats were detected by oil red O and hematoxylin-eosin (HE) stainings. The expression of Nrf2 in rat liver was examined through immunohistochemistry. The level of 8-iso-prostaglandin F2α in serum was detected through enzyme linked immunosorbent assay (ELISA). The mRNA and protein levels of Nrf2 and other related factors in liver tissue were measured by real-time reverse transcriptionpolymerase chain reaction and western blot.
Results
Lipid deposition, hepatic steatosis, focal necrosis in lobular inflammation and ballooning degeneration were emerged in livers of NASH rats. The 8-iso-prostaglandin F2α in the serum of NASH rats increased significantly compared with the control group (
P
<0.05). The mRNA of Nrf2, hemeoxyenase1 (HO-1) and the mRNA and protein levels of quinine oxidoreductase (NQO1) in NASH rats liver tissue showed a striking increase, while the mRNA levels of Keap1, r-glutamylcysteine synthethase (rGCS) and glutathione S-transferase (GST) were significantly decreased compared with the control group (
P
<0.05). After TFHL treatment, 8-iso-prostaglandin F2α level in serum significantly decreased, and Nrf2 mRNA and protein levels in hepatocytes nucleus enhanced compared with the model group (
P
<0.05 or 0.01). Meanwhile the Keap1 mRNA, the mRNA and protein levels of HO-1, NQO1 antibody, rGCS antibody, GST increased after TFHL treatment (
P
<0.05 or 0.01).
Conclusions
Nrf2 and other related factors were involved in development of NASH, and they also served as an important part in its occurrence. By regulating expression of Nrf2 and other related factors, TFHL may play a role in antioxidative stress and prevention of NASH.</description><identifier>ISSN: 1672-0415</identifier><identifier>EISSN: 1993-0402</identifier><identifier>DOI: 10.1007/s11655-016-2450-0</identifier><identifier>PMID: 26919834</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Animals ; Cell Nucleus - drug effects ; Cell Nucleus - metabolism ; Crataegus - chemistry ; Dinoprost - metabolism ; Flavones - pharmacology ; Flavones - therapeutic use ; Lipids - chemistry ; Liver - drug effects ; Liver - metabolism ; Liver - pathology ; Medicine ; Medicine & Public Health ; NF-E2-Related Factor 2 - genetics ; NF-E2-Related Factor 2 - metabolism ; Non-alcoholic Fatty Liver Disease - drug therapy ; Non-alcoholic Fatty Liver Disease - genetics ; Non-alcoholic Fatty Liver Disease - pathology ; Original Article ; Phytotherapy ; Plant Leaves - chemistry ; Rats, Sprague-Dawley ; RNA, Messenger - genetics ; RNA, Messenger - metabolism</subject><ispartof>Chinese journal of integrative medicine, 2018-04, Vol.24 (4), p.265-271</ispartof><rights>Chinese Association of the Integration of Traditional and Western Medicine 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c344t-83b0030be1b0dbf529187e0f35a064d16d214063f7098d97cc51f25e87f6a1253</citedby><cites>FETCH-LOGICAL-c344t-83b0030be1b0dbf529187e0f35a064d16d214063f7098d97cc51f25e87f6a1253</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11655-016-2450-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11655-016-2450-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26919834$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, De-jun</creatorcontrib><creatorcontrib>Cai, Yue-qin</creatorcontrib><creatorcontrib>Pan, Shui-zhen</creatorcontrib><creatorcontrib>Zhang, Li-zong</creatorcontrib><creatorcontrib>Chen, Yun-xiang</creatorcontrib><creatorcontrib>Chen, Fang-ming</creatorcontrib><creatorcontrib>Jin, Ming</creatorcontrib><creatorcontrib>Yan, Mao-xiang</creatorcontrib><creatorcontrib>Li, Xiao-dong</creatorcontrib><creatorcontrib>Chen, Zhi-yun</creatorcontrib><title>Effect of Total Flavone of Haw Leaves on Nuclear Factor Erythroid-2 Related Factor and Other Related Factors in Nonalcoholic Steatohepatitis Rats</title><title>Chinese journal of integrative medicine</title><addtitle>Chin. J. Integr. Med</addtitle><addtitle>Chin J Integr Med</addtitle><description>Objective
To investigate the effect of total flavone of haw leaves (TFHL) on the expression of nuclear factor erythroid-2 related factor (Nrf2) and other related factors in nonalcoholic steatohepatitis (NASH) rats induced by high-fat diet and then to further discuss the mechanism of TFHL’s prevention against NASH.
Methods
High-fat diet was fed to 40 rats to establish the NASH model. Then model rats were intragastrically administrated with 40, 80, 160 mg/(kg•day) TFHL, respectively. The pathological changes of liver tissues in NASH rats were detected by oil red O and hematoxylin-eosin (HE) stainings. The expression of Nrf2 in rat liver was examined through immunohistochemistry. The level of 8-iso-prostaglandin F2α in serum was detected through enzyme linked immunosorbent assay (ELISA). The mRNA and protein levels of Nrf2 and other related factors in liver tissue were measured by real-time reverse transcriptionpolymerase chain reaction and western blot.
Results
Lipid deposition, hepatic steatosis, focal necrosis in lobular inflammation and ballooning degeneration were emerged in livers of NASH rats. The 8-iso-prostaglandin F2α in the serum of NASH rats increased significantly compared with the control group (
P
<0.05). The mRNA of Nrf2, hemeoxyenase1 (HO-1) and the mRNA and protein levels of quinine oxidoreductase (NQO1) in NASH rats liver tissue showed a striking increase, while the mRNA levels of Keap1, r-glutamylcysteine synthethase (rGCS) and glutathione S-transferase (GST) were significantly decreased compared with the control group (
P
<0.05). After TFHL treatment, 8-iso-prostaglandin F2α level in serum significantly decreased, and Nrf2 mRNA and protein levels in hepatocytes nucleus enhanced compared with the model group (
P
<0.05 or 0.01). Meanwhile the Keap1 mRNA, the mRNA and protein levels of HO-1, NQO1 antibody, rGCS antibody, GST increased after TFHL treatment (
P
<0.05 or 0.01).
Conclusions
Nrf2 and other related factors were involved in development of NASH, and they also served as an important part in its occurrence. By regulating expression of Nrf2 and other related factors, TFHL may play a role in antioxidative stress and prevention of NASH.</description><subject>Animals</subject><subject>Cell Nucleus - drug effects</subject><subject>Cell Nucleus - metabolism</subject><subject>Crataegus - chemistry</subject><subject>Dinoprost - metabolism</subject><subject>Flavones - pharmacology</subject><subject>Flavones - therapeutic use</subject><subject>Lipids - chemistry</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>NF-E2-Related Factor 2 - genetics</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Non-alcoholic Fatty Liver Disease - drug therapy</subject><subject>Non-alcoholic Fatty Liver Disease - genetics</subject><subject>Non-alcoholic Fatty Liver Disease - pathology</subject><subject>Original Article</subject><subject>Phytotherapy</subject><subject>Plant Leaves - chemistry</subject><subject>Rats, Sprague-Dawley</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><issn>1672-0415</issn><issn>1993-0402</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1v1DAQtRBVW0p_ABfkI5fAjBM7yRFVuxRpRaW2nC3HGbOpvPFiO0X9GfxjvNqWAwdO8zTv4_AeY-8QPiJA-ykhKikrQFWJRkIFr9g59n1dQQPidcGqFQWjPGNvUnoAkK0CecrOhOqx7-rmnP1eOUc28-D4fcjG87U3j2Gmw-Pa_OIbMo-UeJj5t8V6MpGvjc0h8lV8ytsYprES_Ja8yTS-UGYe-U3eUvyHSHwqMWE23oZt8JPld5lMDlvamzzlKfFbk9NbduKMT3T5fC_Y9_Xq_uq62tx8-Xr1eVPZumly1dUDQA0D4QDj4KTosWsJXC0NqGZENQpsQNWuhb4b-9ZaiU5I6lqnDApZX7APx9x9DD8XSlnvpmTJezNTWJLGTiglO-iwSPEotTGkFMnpfZx2Jj5pBH1YQh-X0GUJfVhCQ_G8f45fhh2Nfx0v1ReBOApSoeYfFPVDWGIpJ_0n9Q-255Oi</recordid><startdate>20180401</startdate><enddate>20180401</enddate><creator>Wang, De-jun</creator><creator>Cai, Yue-qin</creator><creator>Pan, Shui-zhen</creator><creator>Zhang, Li-zong</creator><creator>Chen, Yun-xiang</creator><creator>Chen, Fang-ming</creator><creator>Jin, Ming</creator><creator>Yan, Mao-xiang</creator><creator>Li, Xiao-dong</creator><creator>Chen, Zhi-yun</creator><general>Springer Berlin Heidelberg</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20180401</creationdate><title>Effect of Total Flavone of Haw Leaves on Nuclear Factor Erythroid-2 Related Factor and Other Related Factors in Nonalcoholic Steatohepatitis Rats</title><author>Wang, De-jun ; Cai, Yue-qin ; Pan, Shui-zhen ; Zhang, Li-zong ; Chen, Yun-xiang ; Chen, Fang-ming ; Jin, Ming ; Yan, Mao-xiang ; Li, Xiao-dong ; Chen, Zhi-yun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c344t-83b0030be1b0dbf529187e0f35a064d16d214063f7098d97cc51f25e87f6a1253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Cell Nucleus - drug effects</topic><topic>Cell Nucleus - metabolism</topic><topic>Crataegus - chemistry</topic><topic>Dinoprost - metabolism</topic><topic>Flavones - pharmacology</topic><topic>Flavones - therapeutic use</topic><topic>Lipids - chemistry</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>NF-E2-Related Factor 2 - genetics</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Non-alcoholic Fatty Liver Disease - drug therapy</topic><topic>Non-alcoholic Fatty Liver Disease - genetics</topic><topic>Non-alcoholic Fatty Liver Disease - pathology</topic><topic>Original Article</topic><topic>Phytotherapy</topic><topic>Plant Leaves - chemistry</topic><topic>Rats, Sprague-Dawley</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, De-jun</creatorcontrib><creatorcontrib>Cai, Yue-qin</creatorcontrib><creatorcontrib>Pan, Shui-zhen</creatorcontrib><creatorcontrib>Zhang, Li-zong</creatorcontrib><creatorcontrib>Chen, Yun-xiang</creatorcontrib><creatorcontrib>Chen, Fang-ming</creatorcontrib><creatorcontrib>Jin, Ming</creatorcontrib><creatorcontrib>Yan, Mao-xiang</creatorcontrib><creatorcontrib>Li, Xiao-dong</creatorcontrib><creatorcontrib>Chen, Zhi-yun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Chinese journal of integrative medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, De-jun</au><au>Cai, Yue-qin</au><au>Pan, Shui-zhen</au><au>Zhang, Li-zong</au><au>Chen, Yun-xiang</au><au>Chen, Fang-ming</au><au>Jin, Ming</au><au>Yan, Mao-xiang</au><au>Li, Xiao-dong</au><au>Chen, Zhi-yun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of Total Flavone of Haw Leaves on Nuclear Factor Erythroid-2 Related Factor and Other Related Factors in Nonalcoholic Steatohepatitis Rats</atitle><jtitle>Chinese journal of integrative medicine</jtitle><stitle>Chin. J. Integr. Med</stitle><addtitle>Chin J Integr Med</addtitle><date>2018-04-01</date><risdate>2018</risdate><volume>24</volume><issue>4</issue><spage>265</spage><epage>271</epage><pages>265-271</pages><issn>1672-0415</issn><eissn>1993-0402</eissn><abstract>Objective
To investigate the effect of total flavone of haw leaves (TFHL) on the expression of nuclear factor erythroid-2 related factor (Nrf2) and other related factors in nonalcoholic steatohepatitis (NASH) rats induced by high-fat diet and then to further discuss the mechanism of TFHL’s prevention against NASH.
Methods
High-fat diet was fed to 40 rats to establish the NASH model. Then model rats were intragastrically administrated with 40, 80, 160 mg/(kg•day) TFHL, respectively. The pathological changes of liver tissues in NASH rats were detected by oil red O and hematoxylin-eosin (HE) stainings. The expression of Nrf2 in rat liver was examined through immunohistochemistry. The level of 8-iso-prostaglandin F2α in serum was detected through enzyme linked immunosorbent assay (ELISA). The mRNA and protein levels of Nrf2 and other related factors in liver tissue were measured by real-time reverse transcriptionpolymerase chain reaction and western blot.
Results
Lipid deposition, hepatic steatosis, focal necrosis in lobular inflammation and ballooning degeneration were emerged in livers of NASH rats. The 8-iso-prostaglandin F2α in the serum of NASH rats increased significantly compared with the control group (
P
<0.05). The mRNA of Nrf2, hemeoxyenase1 (HO-1) and the mRNA and protein levels of quinine oxidoreductase (NQO1) in NASH rats liver tissue showed a striking increase, while the mRNA levels of Keap1, r-glutamylcysteine synthethase (rGCS) and glutathione S-transferase (GST) were significantly decreased compared with the control group (
P
<0.05). After TFHL treatment, 8-iso-prostaglandin F2α level in serum significantly decreased, and Nrf2 mRNA and protein levels in hepatocytes nucleus enhanced compared with the model group (
P
<0.05 or 0.01). Meanwhile the Keap1 mRNA, the mRNA and protein levels of HO-1, NQO1 antibody, rGCS antibody, GST increased after TFHL treatment (
P
<0.05 or 0.01).
Conclusions
Nrf2 and other related factors were involved in development of NASH, and they also served as an important part in its occurrence. By regulating expression of Nrf2 and other related factors, TFHL may play a role in antioxidative stress and prevention of NASH.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>26919834</pmid><doi>10.1007/s11655-016-2450-0</doi><tpages>7</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1672-0415 |
ispartof | Chinese journal of integrative medicine, 2018-04, Vol.24 (4), p.265-271 |
issn | 1672-0415 1993-0402 |
language | eng |
recordid | cdi_proquest_miscellaneous_1826658081 |
source | MEDLINE; SpringerLink Journals; Alma/SFX Local Collection |
subjects | Animals Cell Nucleus - drug effects Cell Nucleus - metabolism Crataegus - chemistry Dinoprost - metabolism Flavones - pharmacology Flavones - therapeutic use Lipids - chemistry Liver - drug effects Liver - metabolism Liver - pathology Medicine Medicine & Public Health NF-E2-Related Factor 2 - genetics NF-E2-Related Factor 2 - metabolism Non-alcoholic Fatty Liver Disease - drug therapy Non-alcoholic Fatty Liver Disease - genetics Non-alcoholic Fatty Liver Disease - pathology Original Article Phytotherapy Plant Leaves - chemistry Rats, Sprague-Dawley RNA, Messenger - genetics RNA, Messenger - metabolism |
title | Effect of Total Flavone of Haw Leaves on Nuclear Factor Erythroid-2 Related Factor and Other Related Factors in Nonalcoholic Steatohepatitis Rats |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T05%3A23%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effect%20of%20Total%20Flavone%20of%20Haw%20Leaves%20on%20Nuclear%20Factor%20Erythroid-2%20Related%20Factor%20and%20Other%20Related%20Factors%20in%20Nonalcoholic%20Steatohepatitis%20Rats&rft.jtitle=Chinese%20journal%20of%20integrative%20medicine&rft.au=Wang,%20De-jun&rft.date=2018-04-01&rft.volume=24&rft.issue=4&rft.spage=265&rft.epage=271&rft.pages=265-271&rft.issn=1672-0415&rft.eissn=1993-0402&rft_id=info:doi/10.1007/s11655-016-2450-0&rft_dat=%3Cproquest_cross%3E1826658081%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1826658081&rft_id=info:pmid/26919834&rfr_iscdi=true |