{"title":"Flavonoids as therapeutics for myocardial ischemia-reperfusion injury: a comprehensive review on preclinical studies.","authors":"Vipin Kumar Verma, Priya Bhardwaj, Vaishali Prajapati, Avantika Bhatia, Sayani Purkait, Dharamvir Singh Arya","doi":"10.1186/s42826-024-00218-2","DOIUrl":"10.1186/s42826-024-00218-2","url":null,"abstract":"<p><p>Ischemic heart disease is the most prevalent cause of death worldwide affecting both the gender of all age groups. The high mortality rate is due to damage of myocardial tissue that emanates at the time of myocardial ischemia and re-oxygenation, thus averting reperfusion injury is recognized as a potential way to reduce acute cardiac injury and subsequent mortality. Flavonoids are polyphenol derivatives of plant origin and empirical shreds of evidence substantiate their numerous activities such as antioxidant, anti-inflammatory, anti-apoptotic, and anti-thrombotic activity, leading to their role in cardio protection. Recent investigations have unveiled the capacity of flavonoids to impede pivotal regulatory enzymes, signaling molecules, and transcription factors that orchestrate the mediators participating in the inflammatory cascade. The present comprehensive review, dwells on the preclinical studies on the effectiveness of flavonoids from the year 2007 to 2023, for the prevention and therapeutics for myocardial ischemia-reperfusion injury.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"40 1","pages":"32"},"PeriodicalIF":2.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11376054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Po-Yi Lue, Mark H Oliver, Michel Neef, Peter R Thorne, Haruna Suzuki-Kerr
{"title":"Correction: Sheep as a large animal model for hearing research: comparison to common laboratory animals and humans.","authors":"Po-Yi Lue, Mark H Oliver, Michel Neef, Peter R Thorne, Haruna Suzuki-Kerr","doi":"10.1186/s42826-024-00217-3","DOIUrl":"10.1186/s42826-024-00217-3","url":null,"abstract":"","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"40 1","pages":"31"},"PeriodicalIF":2.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11350983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nontobeko M Gumede, Busisani W Lembede, Pilani Nkomozepi, Richard L Brooksbank, Kennedy H Erlwanger, Eliton Chivandi
{"title":"Protective effect of β-sitosterol against high-fructose diet-induced oxidative stress, and hepatorenal derangements in growing female sprague-dawley rats.","authors":"Nontobeko M Gumede, Busisani W Lembede, Pilani Nkomozepi, Richard L Brooksbank, Kennedy H Erlwanger, Eliton Chivandi","doi":"10.1186/s42826-024-00215-5","DOIUrl":"10.1186/s42826-024-00215-5","url":null,"abstract":"<p><strong>Background: </strong>Chronic consumption of a high-fructose diet causes oxidative stress that compromises kidney and liver health. β-sitosterol (Bst), a phytosterol, is a functional nutrient with health benefits. β-sitosterol antioxidant activity protects the liver and kidney from ROS-mediated damage and lipid peroxidation. We evaluated the potential renoprotective and hepatoprotective effects of orally administrated β-sitosterol in high-fructose diet-fed growing female rats. Thirty-five 21-day old female Sprague-Dawley rat pups were randomly assigned to and administered the following treatments for 12 weeks: group I- standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II- SRC + 20% w/v fructose solution (FS) as drinking fluid + PC; group III- SRC + FS + 100 mg/kg body mass (BM) fenofibrate in gelatine cube; group IV- SRC + FS + 20 mg/kg BM β-sitosterol gelatine cube (Bst) and group V- SRC + PW + Bst. The rats were fasted overnight, weighed then euthanised. Blood was collected, centrifuged and plasma harvested. Livers and kidneys were excised, weighed and samples preserved for histological assessments. Plasma biomarkers of oxidative stress, liver and kidney function and renal tubular injury were assessed.</p><p><strong>Results: </strong>High fructose diet fed rats had increased plasma KIM-1, NGAL (p < 0.001) and MDA levels (p < 0.05). Dietary fructose caused microvesicular and macrovesicular steatosis, and reduced glomerular density, Bowman's capsule area and urinary space. β-sitosterol protected against the high-fructose diet-induced hepatic steatosis and glomerular disturbances without adverse effects on liver and kidney function.</p><p><strong>Conclusions: </strong>β-sitosterol, as a dietary supplement, could potentially be exploited to prevent high-fructose diet-induced NAFLD and to protect against high-fructose diet-induced renal tubular injury.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"40 1","pages":"30"},"PeriodicalIF":2.7,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Payal Bajaj, Tajpreet Kaur, Amrit Pal Singh, Gurcharan Kaur
{"title":"Acute sleep deprivation-induced hepatotoxicity and dyslipidemia in middle-aged female rats and its amelioration by butanol extract of Tinospora cordifolia.","authors":"Payal Bajaj, Tajpreet Kaur, Amrit Pal Singh, Gurcharan Kaur","doi":"10.1186/s42826-024-00216-4","DOIUrl":"10.1186/s42826-024-00216-4","url":null,"abstract":"<p><strong>Background: </strong>Sleep deprivation (SD) due to an unhealthy lifestyle poses an oxidative challenge and is closely associated with an increased risk and prevalence of different metabolic disorders. Although the negative consequences of SD are well reported on mental health little is known about its detrimental effects on liver function and lipid metabolism. Tinospora cordifolia is reported for its hepatoprotective activity in different pre-clinical model systems. The current study was designed to elucidate the cumulative effects of aging and acute SD on liver functions, oxidative stress, and lipid metabolism, and their management by butanol extract of T. cordifolia (B-TCE) using middle-aged female acyclic rats as the model system.</p><p><strong>Results: </strong>Rats were divided into 4 groups: (1) Vehicle-undisturbed (VUD) (2) Vehicle-sleep deprived (VSD) (3) B-TCE pre-treated sleep-deprived (TSD) (4) B-TCE pre-treated undisturbed sleep (TUD). TSD and TUD groups were given 35 mg/kg of B-TCE once daily for 15 days followed by 12 h of sleep deprivation (6 a.m.-6 p.m.) of VSD and TSD group animals using the gentle-handling method while VUD and TUD group animals were left undisturbed. SD of VSD group animals increased oxidative stress, liver function disruption, and dyslipidemia which were ameliorated by B-TCE pre-treatment. Further, B-TCE was observed to target AMPK and its downstream lipid metabolism pathways as well as the p-Akt/cyclinD1/p-bad pathway of cell survival as possible underlying mechanisms of its hepatoprotective activity.</p><p><strong>Conclusions: </strong>These findings suggest that B-TCE being a multi-component extract may be a potential agent in curtailing sleep-related problems and preventing SD-associated hepatotoxicity and dyslipidemia in postmenopausal women.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"40 1","pages":"29"},"PeriodicalIF":2.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Keun Bon Ku, Jihwan Chae, Won Hyung Park, Jeongwoo La, Seung S Lee, Heung Kyu Lee
{"title":"Assessment of immunopathological responses of a novel non-chemical biocide in C57BL/6 for safe disinfection usage.","authors":"Keun Bon Ku, Jihwan Chae, Won Hyung Park, Jeongwoo La, Seung S Lee, Heung Kyu Lee","doi":"10.1186/s42826-024-00214-6","DOIUrl":"10.1186/s42826-024-00214-6","url":null,"abstract":"<p><strong>Background: </strong>Water electrospray technology has been developed and extensively studied for its physical properties and potential application as a non-chemical biocide against airborne pathogens. However, there are still concerns regarding the safety and potential toxicity of inhaling water electrospray (WE) particles. To address these potential hazards and offer insights into the impact of WE on humans, we analyzed the immunopathological response to WE by employing an intranasal challenge C57BL/6 mouse model. This analysis aimed to compare the effects of WE with those of sodium hypochlorite (SH), a well-known biocidal agent.</p><p><strong>Results: </strong>The study findings suggest that the WE did not trigger any pathological immune reactions in the intranasal-challenged C57BL/6 mouse model. Mice challenged with WE did not experience body weight loss, and there was no increase in inflammatory cytokine production compared to SH-treated mice. Histopathological analysis revealed that WE did not cause any damage to the lung tissue. In contrast, mice treated with SH exhibited significant lung tissue damage, characterized by the infiltration of neutrophils and eosinophils. Transcriptomic analysis of lung tissue further confirmed the absence of a pathological immune response in mice treated with WE compared to those treated with SH. Upon intranasal challenge with WE, the C57BL/6 mouse model did not show any evidence of immunopathological damage.</p><p><strong>Conclusions: </strong>The results of this study suggest that WE is a safe technology for disinfecting airborne pathogens. It demonstrated little to no effect on immune system activation and pathological outcomes in the intranasal challenge C57BL/6 mouse model. These findings not only support the potential use of WE as an effective and safe method for air disinfection but also highlight the value of the intranasal challenge of the C57BL/6 mouse model in providing significant immunopathological insights for assessing the inhalation of novel materials for potential use.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"40 1","pages":"28"},"PeriodicalIF":2.7,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tuvshintugs Baljinnyam, Satoshi Fukuda, Yosuke Niimi, Donald Prough, Perenlei Enkhbaatar
{"title":"Combined treatment with vitamin C, hydrocortisone and thiamine does not attenuate morbidity and mortality of septic sheep.","authors":"Tuvshintugs Baljinnyam, Satoshi Fukuda, Yosuke Niimi, Donald Prough, Perenlei Enkhbaatar","doi":"10.1186/s42826-024-00213-7","DOIUrl":"10.1186/s42826-024-00213-7","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is associated with a highest mortality rate in the ICU. Present study tests the efficacy of combined therapy with vitamin C, hydrocortisone and thiamine (combined therapy) in the ovine model of sepsis induced by Pseudomonas aeruginosa. In this study, sepsis was induced in sheep by instillation of Pseudomonas aeruginosa (1 × 10<sup>11</sup> CFU) into the lungs via bronchoscope, under anesthesia. Nine hours after injury, intravenous infusion of vitamin C (0.75 g every 6 h), hydrocortisone (25 mg every 6 h), and thiamine (100 mg every 12 h) or saline was given to the treatment and control groups. Cardiopulmonary variables were recorded.</p><p><strong>Results: </strong>The survival rate was 16.7% in control and 33.3% in treatment groups. In the control group, mean arterial pressure dropped from 93.6 ± 8.6 to 75.5 ± 9.7 mmHg by 9 h, which was not affected by the combined therapy. Pulmonary dysfunction was not attenuated by the combined therapy either. The combined therapy had no effect on increased extravascular lung water content and fluid effusion into thoracic cavity. The bacterial number in the bronchoalveolar lavage fluid was significantly increased in the treatment group than the control group. The blood bacterial number remained comparable between groups.</p><p><strong>Conclusions: </strong>Combined vitamin C, hydrocortisone, and thiamine did not attenuate severity of ovine sepsis.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"40 1","pages":"27"},"PeriodicalIF":2.7,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nerea Huertos Soto, Juan Manuel Gómez Cervantes, María Jesús Fernández Aceñero, María Del Carmen Soto Beauregard
{"title":"Cannabidiol decreases histological intestinal injury in a neonatal experimental model of necrotizing enterocolitis.","authors":"Nerea Huertos Soto, Juan Manuel Gómez Cervantes, María Jesús Fernández Aceñero, María Del Carmen Soto Beauregard","doi":"10.1186/s42826-024-00211-9","DOIUrl":"10.1186/s42826-024-00211-9","url":null,"abstract":"<p><strong>Background: </strong>Necrotizing enterocolitis (NEC) is a severe inflammatory bowel disease in neonates. Our group has developed an experimental model of NEC, with an effectiveness of 73%. Cannabidiol (CBD) is an innovative treatment for neonatal cerebral hypoxic-ischemic pathologies due to its neuroprotective effect, as a potent anti-inflammatory and reducing oxidative stress substance. Our aim was to evaluate the effect of CBD on intestinal lesions in an experimental model of NEC.</p><p><strong>Results: </strong>Mortality and intestinal histological damage was significantly lower in the CBD group compared to the rest (p<0.05), establishing CBD as a protective factor against the development of NEC (OR=0.0255; 95% CI=0.0015-0.4460). At IHQ level (TUNEL technique), a lower cell death rate was also observed in the CBD group compared to the VEH group (p<0.05).</p><p><strong>Conclusions: </strong>In our experimental model, intraperitoneal CBD acts as a protective factor against NEC, resulting in less histological damage and a lower rate of intestinal cell death.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"40 1","pages":"26"},"PeriodicalIF":2.7,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11209976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alina Bilyalova, Airat Bilyalov, Nikita Filatov, Elena Shagimardanova, Andrey Kiyasov, Maria Vorontsova, Oleg Gusev
{"title":"Non-classical animal models for studying adrenal diseases: advantages, limitations, and implications for research.","authors":"Alina Bilyalova, Airat Bilyalov, Nikita Filatov, Elena Shagimardanova, Andrey Kiyasov, Maria Vorontsova, Oleg Gusev","doi":"10.1186/s42826-024-00212-8","DOIUrl":"10.1186/s42826-024-00212-8","url":null,"abstract":"<p><p>The study of adrenal disorders is a key component of scientific research, driven by the complex innervation, unique structure, and essential functions of the adrenal glands. This review explores the use of non-traditional animal models for studying congenital adrenal hyperplasia. It highlights the advantages, limitations, and relevance of these models, including domestic ferrets, dogs, guinea pigs, golden hamsters, pigs, and spiny mice. We provide a detailed analysis of the histological structure, steroidogenesis pathways, and genetic characteristics of these animal models. The morphological and functional similarities between the adrenal glands of spiny mice and humans highlight their potential as an important avenue for future research.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"40 1","pages":"25"},"PeriodicalIF":2.7,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jie Zhai, Auriole Tamegnon, Mei Jiang, Renganayaki Krishna Pandurengan, Edwin Roger Parra
{"title":"Immune profiling of mouse lung adenocarcinoma paraffin tissues using multiplex immunofluorescence panel: a pilot study.","authors":"Jie Zhai, Auriole Tamegnon, Mei Jiang, Renganayaki Krishna Pandurengan, Edwin Roger Parra","doi":"10.1186/s42826-024-00210-w","DOIUrl":"10.1186/s42826-024-00210-w","url":null,"abstract":"<p><strong>Background: </strong>Immune profiling has become an important tool for identifying predictive, prognostic and response biomarkers for immune checkpoint inhibitors from tumor microenvironment (TME). We aimed to build a multiplex immunofluorescence (mIF) panel to apply to formalin-fixed and paraffin-embedded tissues in mice tumors and to explore the programmed cell death protein 1/ programmed cell death 1 ligand 1 (PD-1/PD-L1) axis.</p><p><strong>Results: </strong>An automated eight-color mIF panel was evaluated to study the TME using seven antibodies, including cytokeratin 19, CD3e, CD8a, CD4, PD-1, PD-L1, F4-80 and DAPI, then was applied in six mice lung adenocarcinoma samples. Cell phenotypes were quantified by software to explore the co-localization and spatial distribution between immune cells within the TME. This mice panel was successfully optimized and applied to a small cohort of mice lung adenocarcinoma cases. Image analysis showed a sparse degree of immune cell expression pattern in this cohort. From the spatial analysis we found that T cells and macrophages expressing PD-L1 were close to the malignant cells and other immune cells.</p><p><strong>Conclusions: </strong>Comprehensive immune profiling using mIF in translational studies improves our ability to correlate the PD-1/PD-L1 axis and spatial distribution of lymphocytes and macrophages in mouse lung cancer cells to provide new cues for immunotherapy, that can be translated to human tumors for cancer intervention.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"40 1","pages":"24"},"PeriodicalIF":2.9,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11177412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael A Leninsky, Vladislav E Sobolev, Margarita O Sokolova, Natalya G Voitenko, Nikita V Skvortsov
{"title":"Quantification of 11 metabolites in rat urine after exposure to organophosphates.","authors":"Michael A Leninsky, Vladislav E Sobolev, Margarita O Sokolova, Natalya G Voitenko, Nikita V Skvortsov","doi":"10.1186/s42826-024-00209-3","DOIUrl":"10.1186/s42826-024-00209-3","url":null,"abstract":"<p><strong>Background: </strong>The aim of the study was to develop a technique for quantitative determination of rat urine metabolites by HPLC-MS/MS, which can be used to search for biomarkers of acute intoxication with organophosphates (OPs).</p><p><strong>Results: </strong>The content of metabolites in the urine of rats exposed to a single dose of paraoxon (POX1x); interval, twice daily administration of paraoxon (POX2x); exposure to 2-(o-cresyl)-4H-1, 3, 2-benzodioxaphosphorin-2-oxide and paraoxon (CBPOX) was investigated. New data were obtained on the content in the urine of intact rats as well as rats in 3 models of OP poisoning: 3-methylhistidine, threonine, creatine, creatinine, lactic acid, acetylcarnitine, inosine, hypoxanthine, adenine, 3-hydroxymethyl-butyrate and 2-hydroxymethyl-butyrate.</p><p><strong>Conclusions: </strong>The proposed assay procedure is a simple and reliable tool for urine metabolomic studies. Within 1-3 days after OP exposure in all three models of acute intoxication, the concentration of metabolites in rat urine, with the exception of adenine, changes similarly and symmetrically, regardless of the method of poisoning modeling, in all three models of acute intoxication. Further studies are needed to determine the specificity and reliability of using urinary metabolite concentration changes as potential biomarkers of acute organophosphate intoxication.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"40 1","pages":"23"},"PeriodicalIF":2.9,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11155157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}