Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

The Xiaogu San Attenuates Pain and Cartilage Damage in Rats with Monosodium Iodoacetate Induced Osteoarthritis

Author(s): Xiaoyun Zhang, Rilan Chen*, Zilong Liao, Ying Zhu, Yueping Chen, Jianhang Liu and Xia Chen

Volume 25, Issue 11, 2022

Published on: 11 January, 2022

Page: [1914 - 1951] Pages: 38

DOI: 10.2174/1386207325666211008130312

Price: $65

Abstract

Background: Osteoarthritis (OA) is a degenerative joint disease with an increasing incidence associated with increased life expectancy. The application of traditional Chinese medicine in the treatment of OA has become a research hotspot.

Objective: This study investigated the effects of XGS externally applied to osteoarthritic joints and analyze its effect on pain in monosodium iodoacetate (MIA)-induced OA rats. This study also evaluates potential mechanisms behind the anti-osteoarthritic effects of XGS.

Methods: A total of 24 Sprague Dawley rats were evenly and randomly divided into three separate groups, including the normal control (NC), OA and XGS groups. MIA (50 μL, 10 mg/mL) was injected into the left knee joints of the rats to induce OA. After 7 days, The rats of XGS group were given XGS (0.45 g) that was externally applied to the left knee joint, were fixed with gauze, and continuously administered XGS for 28 days. Morphological changes in tissues and organs were examined using H&E staining. Biochemical indicators were measured using an automatic biochemical analyzer. Inflammatory cytokines were detected using ELISA kits and immunohistochemistry. RNA-based high-throughput sequencing (RNA-seq) was performed to detect differential expression of mRNAs in normal and MIA–induced OA rats.

Results: Stride of the left leg was extended in rats, matrix increased on cartilage tissue surfaces, and inflammatory cytokines were reduced when treated with XGS. RNA-seq results revealed that the PI3K-Akt signaling pathway is activated in the OA model. The qRT-PCR showed that the expression levels of Tnn, Col6a6, Igf1 and Lamb1 were up-regulated by XGS.

Conclusion: Altogether, this work demonstrated the potential therapeutic effects of XGS in rats with OA induced by MIA. The XGS may be considered an alternative therapy to manage OA.

Keywords: Osteoarthritis, Xiaogu San, PI3K/AKT signaling pathway, pain, cartilage damage, knee joint.

Graphical Abstract

[1]
Ondrésik, M.; Maia, F.; Morais, A.D.S.; Gertrudes, A.; Bacelar, A.; Reis, R.L.; Correia, C. Gon?Alves, C; Radhouani, H; Sousa, R; Oliveira, J Management of knee Osteoarthritis. Current status and future trends. Biotechnol. Bioeng., 2016, 114(4), 717-739.
[http://dx.doi.org/10.1002/bit.26182] [PMID: 27618194]
[2]
Li, G.; Yin, J.; Gao, J.; Cheng, T.S.; Pavlos, N.J.; Zhang, C.; Zheng, M.H. Subchondral bone in osteoarthritis: Insight into risk factors and microstructural changes. Arthritis Res. Ther., 2013, 15(6), 223.
[http://dx.doi.org/10.1186/ar4405] [PMID: 24321104]
[3]
Leong, D.J.; Choudhury, M.; Hirsh, D.M.; Hardin, J.A.; Cobelli, N.J.; Sun, H.B. Nutraceuticals: Potential for chondroprotection and mo-lecular targeting of osteoarthritis. Int. J. Mol. Sci., 2013, 14(11), 23063-23085.
[http://dx.doi.org/10.3390/ijms141123063] [PMID: 24284399]
[4]
Maiese, K. Picking a bone with WISP1 (CCN4): New strategies against degenerative joint disease. J. Transl. Sci., 2016, 1(3), 83-85.
[http://dx.doi.org/10.15761/JTS.1000120] [PMID: 26893943]
[5]
Fauci, A.; Fauci, A.S.; Braunwald, E.; Kasper, D.; Hauser, S.; Dan, L.; Jameson, J.; Loscalzo, J. Harrison’s Principles of Internal Medi-cine; Mcgraw-hill, 2014.
[6]
Jin, C.; Lee, A.; Joong, K.; Goya, C.; Seung-Hyung, K. Protective effects of peucedanum japonicum extract against osteoarthritis in an animal model using a combined systems approach for compound-target prediction. Nutrients, 2018, 10(6), 754.
[7]
Chen, Z.; Li, X-P.; Li, Z-J.; Xu, L.; Li, X-M. Reduced hepatotoxicity by total glucosides of paeony in combination treatment with lefluno-mide and methotrexate for patients with active rheumatoid arthritis. Int. Immunopharmacol., 2013, 15(3), 474-477.
[http://dx.doi.org/10.1016/j.intimp.2013.01.021] [PMID: 23415907]
[8]
Hamidpour, M.; Hamidpour, R.; Hamidpour, S.; Shahlari, M. Chemistry, pharmacology, and medicinal property of sage (salvia) to prevent and cure illnesses such as obesity, diabetes, depression, dementia, lupus, autism, heart disease, and cancer. J. Tradit. Complement. Med., 2014, 4(2), 82-88.
[http://dx.doi.org/10.4103/2225-4110.130373] [PMID: 24860730]
[9]
Maione, F.; Mascolo, N. Danshen and the cardiovascular system: New advances for an old remedy. Semin. Thromb. Hemost., 2016, 42(3), 321-322.
[http://dx.doi.org/10.1055/s-0036-1580086] [PMID: 26951502]
[10]
Chen, Z.; Zhang, C.; Gao, F.; Fu, Q.; Fu, C.; He, Y.; Zhang, J. A systematic review on the rhizome of Ligusticum chuanxiong Hort. (Chuanxiong). Food Chem. Toxicol., 2018, 119, 309-325.
[http://dx.doi.org/10.1016/j.fct.2018.02.050] [PMID: 29486278]
[11]
Zheng, H.P. Clinical observation on the therapeutic effect of percutaneous application of “xiaogu san” (osteophyte-eliminating powder) in the treatment of 105 cases of ankylosing spondylitis. Int. Convention Trad. Med., 2004. Available from: http://223.220.252.164:888/KCMS/detail/detail.aspx?filename=ZYKY200411001739&dbcode=IPFD&dbname=IP FD2006
[12]
Guo, C.L. Ma Bai Xiao Gu San in the treatment of bone hyperplasia. J. Intern. Med., 1993, 04.
[13]
Yang, S.W. Clinical experience in treating 128 cases of osteophytes with Xiao Gu San. Chin. Med. J., 2014, 8, 139-140.
[14]
Tong, L.K.; Huang, J.S. Treatment of 221 cases of bone hyperplasia with Xiao Gu San plus manipulation. Hebei Trad. Chin. Med., 2000, 7, 503-503.
[15]
Kuyinu, E.L.; Narayanan, G.; Nair, L.S.; Laurencin, C.T. Animal models of osteoarthritis: Classification, update, and measurement of outcomes. J. Orthop. Surg. Res., 2016, 11(1), 19.
[http://dx.doi.org/10.1186/s13018-016-0346-5] [PMID: 26837951]
[16]
Piel, M.J.; Kroin, J.S.; van Wijnen, A.J.; Kc, R. Im, H-J. Pain assessment in animal models of osteoarthritis. Gene, 2014, 537(2), 184-188.
[http://dx.doi.org/10.1016/j.gene.2013.11.091] [PMID: 24333346]
[17]
Kullander, K.; Croll, S.D.; Zimmer, M.; Pan, L.; McClain, J.; Hughes, V.; Zabski, S.; DeChiara, T.M.; Klein, R.; Yancopoulos, G.D.; Gale, N.W. Ephrin-B3 is the midline barrier that prevents corticospinal tract axons from recrossing, allowing for unilateral motor control. Genes Dev., 2001, 15(7), 877-888.
[http://dx.doi.org/10.1101/gad.868901] [PMID: 11297511]
[18]
Lin, J.; Hou, Y.; Huang, S.; Wang, Z.; Sun, C.; Wang, Z.; He, X.; Tam, N.L.; Wu, C.; Wu, L. Exportin-T promotes tumor proliferation and invasion in hepatocellular carcinoma. Mol. Carcinog., 2019, 58(2), 293-304.
[http://dx.doi.org/10.1002/mc.22928] [PMID: 30334580]
[19]
Jamieson, S.E.; de Roubaix, L-A.; Cortina-Borja, M.; Tan, H.K.; Mui, E.J.; Cordell, H.J.; Kirisits, M.J.; Miller, E.N.; Peacock, C.S.; Har-grave, A.C.; Coyne, J.J.; Boyer, K.; Bessieres, M-H.; Buffolano, W.; Ferret, N.; Franck, J.; Kieffer, F.; Meier, P.; Nowakowska, D.E.; Paul, M.; Peyron, F.; Stray-Pedersen, B.; Prusa, A-R.; Thulliez, P.; Wallon, M.; Petersen, E.; McLeod, R.; Gilbert, R.E.; Blackwell, J.M. Genetic and epigenetic factors at COL2A1 and ABCA4 influence clinical outcome in congenital toxoplasmosis. PLoS One, 2008, 3(6), e2285-e2285.
[http://dx.doi.org/10.1371/journal.pone.0002285] [PMID: 18523590]
[20]
McAlinden, A.; Majava, M.; Bishop, P.N.; Perveen, R.; Black, G.C.M.; Pierpont, M.E.; Ala-Kokko, L.; Männikkö, M. Missense and non-sense mutations in the alternatively-spliced exon 2 of COL2A1 cause the ocular variant of Stickler syndrome. Hum. Mutat., 2008, 29(1), 83-90.
[http://dx.doi.org/10.1002/humu.20603] [PMID: 17721977]
[21]
Sandell, L.J.; Aigner, T. Articular cartilage and changes in arthritis. An introduction: Cell biology of osteoarthritis. Arthritis Res., 2001, 3(2), 107-113.
[http://dx.doi.org/10.1186/ar148] [PMID: 11178118]
[22]
Goldring, M.B. The role of the chondrocyte in osteoarthritis. Arthritis Rheum., 2000, 43(9), 1916-1926.
[http://dx.doi.org/10.1002/1529-0131(200009)43:9<1916:AID-ANR2>3.0.CO;2-I] [PMID: 11014341]
[23]
Huang, K.; Wu, L.D. Aggrecanase and aggrecan degradation in osteoarthritis: a review. J. Int. Med. Res., 2008, 36(6), 1149-1160.
[http://dx.doi.org/10.1177/147323000803600601] [PMID: 19094423]
[24]
Poole, A.R.; Kobayashi, M.; Yasuda, T.; Laverty, S.; Mwale, F.; Kojima, T.; Sakai, T.; Wahl, C.; El-Maadawy, S.; Webb, G.; Tchetina, E.; Wu, W. Type II collagen degradation and its regulation in articular cartilage in osteoarthritis. Ann. Rheum. Dis., 2002, 61(Suppl. 2), ii78-ii81.
[http://dx.doi.org/10.1136/ard.61.suppl_2.ii78] [PMID: 12379630]
[25]
Ryu, J-H.; Yang, S.; Shin, Y.; Rhee, J.; Chun, C-H.; Chun, J-S. Interleukin-6 plays an essential role in hypoxia-inducible factor 2α-induced experimental osteoarthritic cartilage destruction in mice. Arthritis Rheum., 2011, 63(9), 2732-2743.
[http://dx.doi.org/10.1002/art.30451] [PMID: 21590680]
[26]
Latourte, A.; Cherifi, C.; Maillet, J.; Ea, H-K.; Bouaziz, W.; Funck-Brentano, T.; Cohen-Solal, M.; Hay, E.; Richette, P. Systemic inhibition of IL-6/Stat3 signalling protects against experimental osteoarthritis. Ann. Rheum. Dis., 2017, 76(4), 748-755.
[http://dx.doi.org/10.1136/annrheumdis-2016-209757] [PMID: 27789465]
[27]
Yokota, K.; Sato, K.; Miyazaki, T.; Kitaura, H.; Kayama, H.; Miyoshi, F.; Araki, Y.; Akiyama, Y.; Takeda, K.; Mimura, T. Combination of tumor necrosis factor α and interleukin-6 induces mouse osteoclast-like cells with bone resorption activity both in vitro and in vivo. Arthritis Rheumatol., 2014, 66(1), 121-129.
[http://dx.doi.org/10.1002/art.38218] [PMID: 24431283]
[28]
Rowan, A.D.; Koshy, P.J.; Shingleton, W.D.; Degnan, B.A.; Heath, J.K.; Vernallis, A.B.; Spaull, J.R.; Life, P.F.; Hudson, K.; Cawston, T.E. Synergistic effects of glycoprotein 130 binding cytokines in combination with interleukin-1 on cartilage collagen breakdown. Arthritis Rheum., 2001, 44(7), 1620-1632.
[http://dx.doi.org/10.1002/1529-0131(200107)44:7<1620:AID-ART285>3.0.CO;2-B] [PMID: 11465713]
[29]
Zhang, Q.; Wang, J.; Chen, C.; Kong, Y.; Yan, H.; Duan, J.; Wang, C.; Sha, Y.; Wen, X.; Wang, C. Perfluorooctanoic acid induces migration and invasion and inhibits apoptosis through the PI3K/AKT signaling pathway in human rhabdomyosarcoma cells. Oncol. Rep., 2019, 42(4), 1558-1568.
[http://dx.doi.org/10.3892/or.2019.7265] [PMID: 31524277]
[30]
Chen, J.; Jiang, C.; Fu, L.; Zhu, C.L.; Xiang, Y.Q.; Jiang, L.X.; Chen, Q.; Liu, W.M.; Chen, J.N.; Zhang, L.Y.; Liu, M.; Chen, C.; Tang, H.; Wang, B.; Tsao, S.W.; Kwong, D.L.; Guan, X.Y. CHL1 suppresses tumor growth and metastasis in nasopharyngeal carcinoma by repress-ing PI3K/AKT signaling pathwayvia interaction with Integrin β1 and Merlin. Int. J. Biol. Sci., 2019, 15(9), 1802-1815.
[http://dx.doi.org/10.7150/ijbs.34785] [PMID: 31523184]
[31]
Khan, M.A.; Jain, V.K.; Rizwanullah, M.; Ahmad, J.; Jain, K. PI3K/AKT/mTOR pathway inhibitors in triple-negative breast cancer: a re-view on drug discovery and future challenges. Drug Discov. Today, 2019, 24(11), 2181-2191.
[http://dx.doi.org/10.1016/j.drudis.2019.09.001] [PMID: 31520748]
[32]
Ahmed, S.; Wang, N.; Hafeez, B.B.; Cheruvu, V.K.; Haqqi, T.M. Punica granatum L. extract inhibits IL-1beta-induced expression of ma-trix metalloproteinases by inhibiting the activation of MAP kinases and NF-kappaB in human chondrocytes in vitro. J. Nutr., 2005, 135(9), 2096-2102.
[http://dx.doi.org/10.1093/jn/135.9.2096] [PMID: 16140882]
[33]
Wang, C.; Zeng, L.; Zhang, T.; Liu, J.; Wang, W. Tenuigenin prevents IL-1β-induced inflammation in human osteoarthritis chondrocytes by suppressing PI3K/AKT/NF-κB signaling pathway. Inflammation, 2016, 39(2), 807-812.
[http://dx.doi.org/10.1007/s10753-016-0309-3] [PMID: 26846886]
[34]
Cai, C.; Min, S.; Yan, B.; Liu, W.; Yang, X.; Li, L.; Wang, T.; Jin, A. MiR-27a promotes the autophagy and apoptosis of IL-1β treated-articular chondrocytes in osteoarthritis through PI3K/AKT/mTOR signaling. Aging (Albany NY), 2019, 11(16), 6371-6384.
[http://dx.doi.org/10.18632/aging.102194] [PMID: 31460867]
[35]
Hashimoto, M.; Nakasa, T.; Hikata, T.; Asahara, H. Molecular network of cartilage homeostasis and osteoarthritis. Med. Res. Rev., 2008, 28(3), 464-481.
[http://dx.doi.org/10.1002/med.20113] [PMID: 17880012]
[36]
Vincenti, M.P.; Brinckerhoff, C.E. Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: Integration of complex signaling pathways for the recruitment of gene-specific transcription factors. Arthritis Res., 2002, 4(3), 157-164.
[http://dx.doi.org/10.1186/ar401] [PMID: 12010565]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version384msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[18:04:06] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[18:04:06] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[18:04:06] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[18:04:06] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (145ms)time
  • Application (239ms)time
  • 1 x Application (62.17%)
    239ms
    1 x Booting (37.83%)
    145ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    36 statements were executed, 4 of which were duplicates, 32 unique. Show only duplicated147ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('316589210','',1,1739988246,1739988246) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1739988246
      1.37msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('316589210','/article/118387',1,1739988246,1739988246)
      1.45msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 316589210 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316589210) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 316589210 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316589210) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 316589210 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316589210) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 316589210 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316589210) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 316589210 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316589210) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 316589210 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316589210) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 316589210 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316589210) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 316589210 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316589210) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 316589210 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316589210) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 316589210 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316589210) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 316589210 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316589210) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 316589210 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316589210) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 316589210 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316589210) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 316589210 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316589210) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 316589210 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316589210) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 316589210 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316589210) limit 1
      15.61msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 316589210
      • 1: 316589210
      • 2: 316589210
      • 3: 316589210
      • 4: 316589210
      • 5: 316589210
      • 6: 316589210
      • 7: 316589210
      • 8: 316589210
      • 9: 316589210
      • 10: 316589210
      • 11: 316589210
      • 12: 316589210
      • 13: 316589210
      • 14: 316589210
      • 15: 316589210
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=118387
      700μsalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 8 limit 1
      970μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 8
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=8) and sj.journal_id!=8 group by `j`.`nid`) as `aggregate_table`
      1.32msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=8) and sj.journal_id!=8 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      960μsalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=8) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      5.39msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=8) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      3.54msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '118387'
      990μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 118387
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '118387'
      3.67msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 118387
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '118387' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.52msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 118387
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      280μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      530μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 8 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      29.86msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 8 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      21.96msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 8 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      16.21msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 118387 limit 1
      990μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 118387
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 118387 and content_type = 'article' order by status desc limit 1
      330μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 197095 limit 1
      230μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 197095
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      260μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CCHTS' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      370μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CCHTS
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '118387' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      1.18msalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '11774' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      350μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '3115' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      350μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316589210 and j.to_ip >=316589210 )) and ((j.from_date <= 1739988246 and j.to_date >= 1739988246 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3115) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316589210 and j.to_ip >=316589210 )) and ((j.from_date <= 1739988246 and j.to_date >= 1739988246 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3115) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316589210 and j.to_ip >=316589210 )) and ((j.from_date <= 1739988246 and j.to_date >= 1739988246 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3115)
      24.37msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316589210 and j.to_ip >=316589210 )) and ((j.from_date <= 1739988246 and j.to_date >= 1739988246 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11774) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316589210 and j.to_ip >=316589210 )) and ((j.from_date <= 1739988246 and j.to_date >= 1739988246 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11774) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316589210 and j.to_ip >=316589210 )) and ((j.from_date <= 1739988246 and j.to_date >= 1739988246 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11774)
      950μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316589210 and j.to_ip >=316589210 )) and ((j.from_date <= 1739988246 and j.to_date >= 1739988246 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 118387) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316589210 and j.to_ip >=316589210 )) and ((j.from_date <= 1739988246 and j.to_date >= 1739988246 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 118387) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316589210 and j.to_ip >=316589210 )) and ((j.from_date <= 1739988246 and j.to_date >= 1739988246 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 118387)
      870μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '1914' and is_uploaded = 1 and issue_id = 11774 order by cast(first_page as SIGNED) desc limit 1
      760μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 1914
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '1951' and is_uploaded = 1 and issue_id = 11774 order by cast(first_page as SIGNED) asc limit 1
      650μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 1951
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      250μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      320μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 118387 limit 1
      3.96msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 118387
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 8 and `b`.`banner_from_date` <= 1739988246 and `b`.`banner_to_date` >= 1739988246 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.61msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 8
      • 3: 1739988246
      • 4: 1739988246
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 8 and `b`.`banner_from_date` <= 1739988246 and `b`.`banner_to_date` >= 1739988246 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.64msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 8
      • 3: 1739988246
      • 4: 1739988246
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='52e5be9ebc04847f7c6e35659406c4bb'
      300μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        uzAoide0ZZdQHCkSIV18tn4XDShWLrJ9BgpuL8Bk
        uc_cart_id
        52e5be9ebc04847f7c6e35659406c4bb
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/118387" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/118387
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:8 [ "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Wed, 19 Feb 2025 18:04:06 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkdWbkxOKzF0ZkZqK3FoUUtJaW5VUnc9PSIsInZhbHVlIjoiZU1GQjJ2WkRCSDR0RjRIcm4wc3ZWWG5xaHJ1cnhRNFlZaFB5VUx2Sm1uVHBIN0NER1RlRUoxYmFESHExUVQ3Z1RGd3hlUldzYnBEZmlzRU03L1k4TVk5cERjMlluS2dHajVXL3EwVUpYZXFJVDdFU1VwVkFCU3R1Wm1IVE1iUU8iLCJtYWMiOiIwYzU4MjQ0OWY0NDI4YjBiZTBmMjNiN2M2YWIwMWI0ZjlmMjI0MzNhODliOWNhZTRkOWZmZTYyZjBlZDM3YTYzIiwidGFnIjoiIn0%3D; expires=Sat, 22 Feb 2025 06:04:06 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IkdWbkxOKzF0ZkZqK3FoUUtJaW5VUnc9PSIsInZhbHVlIjoiZU1GQjJ2WkRCSDR0RjRIcm4wc3ZWWG5xaHJ1cnhRNFlZaFB5VUx2Sm1uVHBIN0NER1RlRUoxYmFESHExUVQ3Z1RGd3hlU" 1 => "alphaeurekaselectnet_session=eyJpdiI6InJsWVljVjdjV1R5KzdhUkhrOGRjQkE9PSIsInZhbHVlIjoiL3hReEovNmhiSTYrQ3R1SnJveWR3OVd1Vm5yNk9FajhuMVNyczd4dU9xbGpTaDlMbFdXYTU1aGJGaERTM2o0cVAyVG1VTnV4WGs0dGxzUXBZZ1hKWlRYRlNBMHBEbHJLUDAxUEdBNWRQNjV5RWNKYzRZVzZuM3lVMGIwTGtTZlgiLCJtYWMiOiI1YzM3NWNlM2YyYTYxZjQ4YWIyMzE3NTdlZjkyYmRhOWZhOTM5OTFhYWQwM2Y1YWQ1ZWI4ODNkN2YyYzQ5ZjJkIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6InJsWVljVjdjV1R5KzdhUkhrOGRjQkE9PSIsInZhbHVlIjoiL3hReEovNmhiSTYrQ3R1SnJveWR3OVd1Vm5yNk9FajhuMVNyczd4dU9xbGpTaDlMbFdXYTU1aGJ" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkdWbkxOKzF0ZkZqK3FoUUtJaW5VUnc9PSIsInZhbHVlIjoiZU1GQjJ2WkRCSDR0RjRIcm4wc3ZWWG5xaHJ1cnhRNFlZaFB5VUx2Sm1uVHBIN0NER1RlRUoxYmFESHExUVQ3Z1RGd3hlUldzYnBEZmlzRU03L1k4TVk5cERjMlluS2dHajVXL3EwVUpYZXFJVDdFU1VwVkFCU3R1Wm1IVE1iUU8iLCJtYWMiOiIwYzU4MjQ0OWY0NDI4YjBiZTBmMjNiN2M2YWIwMWI0ZjlmMjI0MzNhODliOWNhZTRkOWZmZTYyZjBlZDM3YTYzIiwidGFnIjoiIn0%3D; expires=Sat, 22-Feb-2025 06:04:06 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IkdWbkxOKzF0ZkZqK3FoUUtJaW5VUnc9PSIsInZhbHVlIjoiZU1GQjJ2WkRCSDR0RjRIcm4wc3ZWWG5xaHJ1cnhRNFlZaFB5VUx2Sm1uVHBIN0NER1RlRUoxYmFESHExUVQ3Z1RGd3hlU" 1 => "alphaeurekaselectnet_session=eyJpdiI6InJsWVljVjdjV1R5KzdhUkhrOGRjQkE9PSIsInZhbHVlIjoiL3hReEovNmhiSTYrQ3R1SnJveWR3OVd1Vm5yNk9FajhuMVNyczd4dU9xbGpTaDlMbFdXYTU1aGJGaERTM2o0cVAyVG1VTnV4WGs0dGxzUXBZZ1hKWlRYRlNBMHBEbHJLUDAxUEdBNWRQNjV5RWNKYzRZVzZuM3lVMGIwTGtTZlgiLCJtYWMiOiI1YzM3NWNlM2YyYTYxZjQ4YWIyMzE3NTdlZjkyYmRhOWZhOTM5OTFhYWQwM2Y1YWQ1ZWI4ODNkN2YyYzQ5ZjJkIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6InJsWVljVjdjV1R5KzdhUkhrOGRjQkE9PSIsInZhbHVlIjoiL3hReEovNmhiSTYrQ3R1SnJveWR3OVd1Vm5yNk9FajhuMVNyczd4dU9xbGpTaDlMbFdXYTU1aGJ" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "uzAoide0ZZdQHCkSIV18tn4XDShWLrJ9BgpuL8Bk" "uc_cart_id" => "52e5be9ebc04847f7c6e35659406c4bb" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/118387" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-19 18:04:06GET/article/118387414361