Xinyuan Ren, Yue Shi, Bo Xiao, Xianbin Su, Hui Shi, Guang He, Peijie Chen, Die Wu, Yi Shi
{"title":"Gene Doping Detection From the Perspective of 3D Genome.","authors":"Xinyuan Ren, Yue Shi, Bo Xiao, Xianbin Su, Hui Shi, Guang He, Peijie Chen, Die Wu, Yi Shi","doi":"10.1002/dta.3850","DOIUrl":"https://doi.org/10.1002/dta.3850","url":null,"abstract":"<p><p>Since the early 20th century, the concept of doping was first introduced. To achieve better athletic performance, chemical substances were used. By the mid-20th century, it became gradually recognized that the illegal use of doping substances can seriously endangered athletes' health and compromised the fairness of sports competitions. Over the past 30 years, the World Anti-Doping Agency (WADA) has established corresponding rules and regulations to prohibit athletes from using doping substances or restrict the use of certain drugs, and isotope, chromatography, and mass spectrometry techniques were accredited to detect doping substances. With the development of gene editing technology, many genetic diseases have been effectively treated, but enabled by the same technology, doping has also the potential to pose a threat to sports in the form of gene doping. WADA has explicitly indicated gene doping in the Prohibited List as a prohibited method (M3) and approved qPCR detection. However, gene doping can easily evade detection, if the target genes' upstream regulatory elements are considered, the task became more challenging. Hi-C experiment driven 3D genome technology, through perspectives such as topologically associating domain (TAD) and chromatin loop, provides a more comprehensive and in-depth understanding of gene regulation and expression, thereby better preventing the potential use of 3D genome level gene doping. In this work, we will explore gene doping from a different perspective by analyzing recent studies on gene doping and explore related genes under 3D genome.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Impact of Triptorelin on Hormone Levels in Human and Its Metabolite Confirmation Using Liquid Chromatography-Ion Trap/Time-of-Flight Mass Spectrometry (LC/MS-IT-TOF) and Liquid Chromatography-Orbitrap (LC-Orbitrap) for Doping Control Analysis.","authors":"Navaporn Saardpun, Cholsittapan Asawesna, Seksun Kaewklam, Premsant Sangkhum, Wisoot Kongchareonsombat, Thanit Kusamran, Darawan Pinthong","doi":"10.1002/dta.3849","DOIUrl":"https://doi.org/10.1002/dta.3849","url":null,"abstract":"<p><p>Triptorelin, a synthetic gonadotrophin-releasing hormone (GnRH), is mainly used in the clinical treatment of prostate cancer. The mechanism initially stimulates luteinizing hormone (LH) and testosterone secretion followed by suppression, resulting in a reduction in cancer progression. However, GnRHs are prohibited in doping control because of the indirect surge of LH and testosterone. Therefore, GnRH analog detection and confirmation are enforced by World Anti-Doping Agency (WADA) requirements. The effects of triptorelin on LH and endogenous steroid levels in urine and serum of five prostate cancer patients taking triptorelin for the first time were investigated and compared with leuprorelin. The samples were collected at 0.0 h, 3.0 h, 6.0 h, 1 month, and 3 months later after drug administration. The effect of triptorelin on LH levels was measured using a sandwich enzyme-linked immunoassay (ELISA). Testosterone and endogenous steroid levels were monitored using gas chromatography coupled with mass spectrometry (GC/MS). Triptorelin showed an advantage over leuprorelin on LH and testosterone suppression, which is preferable to use for prostate cancer treatment. In this study, triptorelin (5-10), a unique in vivo metabolite, was found in urine and serum and verified with synthetic triptorelin (5-10). The metabolite was analyzed using liquid chromatography combined with Orbitrap (LC-Orbitrap) and liquid chromatography coupled with ion trap/time-of-flight mass spectrometry (LC/MS-IT-TOF). When triptorelin levels are undetectable, the presence of triptorelin (5-10) in human urine can be used as evidence that triptorelin is being misused in doping control.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Annual Banned-Substance Review 17th Edition-Analytical Approaches in Human Sports Drug Testing 2023/2024.","authors":"Mario Thevis, Tiia Kuuranne, Hans Geyer","doi":"10.1002/dta.3835","DOIUrl":"https://doi.org/10.1002/dta.3835","url":null,"abstract":"<p><p>The 17th edition of the annual banned-substance review on analytical approaches in human sports drug testing is dedicated to literature published between October 2023 and September 2024. As in previous years, focus is put particularly on new or enhanced analytical options in human doping controls as well as investigations into the metabolism and elimination of compounds of interest, which represent central (while not exclusive) cornerstones of the global anti-doping mission. New information published within the past 12 months on established doping agents as well as new potentially relevant substances are reviewed and discussed in the context of the World Anti-Doping Agency's 2024 Prohibited List. Thereby, analytical challenges, especially with regard to the continuously growing number of target compounds and potentially relevant drug classes as well as the exigency (and consequences) of utmost analytical retrospectivity, are thematized and contextualized. Investigations especially into anabolic agents, peptide hormones, and strategies for the detection of gene doping were identified as core areas of anti-doping research in the reviewed period.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manuela Carla Monti, Melanie Bauer, Konrad Koch, Eva Scheurer, Götz Schlotterbeck
{"title":"Evaluation of ATR-FTIR, HPLC-DAD, GC-MS, and GC-IR for the Analysis of 145 Street Drug Samples From Drug Checking Services.","authors":"Manuela Carla Monti, Melanie Bauer, Konrad Koch, Eva Scheurer, Götz Schlotterbeck","doi":"10.1002/dta.3843","DOIUrl":"https://doi.org/10.1002/dta.3843","url":null,"abstract":"<p><p>Drug checking services (DCS) are entities that allow recreational drug users to have street drug samples analyzed. Diverse analytical methods are applied for DCS, ranging from test strips to mass spectrometry (MS). This work evaluates the performance and utility of common methodologies used for DCS operating with off-site drug testing, while additionally assessing the potential of gas chromatography coupled to vapor phase infrared spectroscopy (GC-IR). Gas chromatography MS (GC-MS), GC-IR, and high-performance liquid chromatography with diode array detector (HPLC-DAD) were evaluated based on the analysis of 145 street drug samples obtained from two Swiss DCS. Additionally, attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) was applied and is briefly discussed. A combined total of 245 analytes (including adulterants and cutting agents) were detected. GC-MS presented the greatest number of detected compounds, with a sensitivity of 96% compared with the sum of all analytes, followed by HPLC-DAD with 82%, while GC-IR showed limited sensitivity with 70%. GC-IR underperformed regarding the detection of low-abundant adulterants and of the main active ingredients in strongly adulterated samples. This study discusses the limitations and strengths of the evaluated methods in the specific context of DCS, while providing insights into the occurrence of false declarations (differing analytical results compared with alleged drug identity) and the distributions of adulterants and cutting agents in street drug samples. Based on our results, complementary approaches are considered the most valuable. Finally, the promotion of comprehensive guidelines regarding the quality and suitability of analytical methods for DCS would be highly desired.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Detection of Oral Testosterone Undecanoate Administration in UGT2B117 del/del and del/ins Individuals. Part I: Urinary Steroid Profile and IRMS Markers.","authors":"Sergi Coll, Sho Shiomura, Élida Alechaga, Claudia Bressan, Núria Monfort, Rosa Ventura, Masato Okano","doi":"10.1002/dta.3846","DOIUrl":"https://doi.org/10.1002/dta.3846","url":null,"abstract":"<p><p>The detection of endogenous anabolic androgenic steroids misuse in Asian population using the Steroidal Module of the Athlete Biological Passport (ABP) is a challenge due to the high prevalence of UGT2B17 gene deletion polymorphism and low levels of testosterone (T) glucuronide. In this study, the capabilities of different approaches based on urine analysis for detecting oral T undecanoate administration were evaluated in 13 Asian volunteers, including 11 subjects with del/del genotype and 2 subjects with del/ins genotype. In this part of the work, the effect on the urinary steroid profile (SP) and the isotope ratio mass spectrometry (IRMS) markers were studied. Results showed that the 5α-androstane-3α,17β-diol/epitestosterone ratio is the most sensitive marker of the SP to detect oral T administration in Asian volunteers. All urines that led to suspicious urinary SP were concluded IRMS positive. However, for some subjects, the ABP Steroidal Module was unable to identify suspicious samples that were still detectable by IRMS. Positive IRMS samples were detected up to 24 h (n = 9), 36 h (n = 3), or 48 h (n = 1) after oral administration. Overall, the urinary SP together with IRMS allowed the detection of T administration in Asian volunteers. However, the detection windows are short, as reported for oral T administration in Caucasian volunteers. These findings highlight the need of implementing additional markers in the Steroidal Module of ABP that could enlarge detection windows.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Detection of Oral Testsosterone Undecanoate Administration in UGT2B17 del/del and del/ins Individuals. Part II: Urinary Endogenous Steroid Sulfate Markers.","authors":"Sergi Coll, Sho Shiomura, Élida Alechaga, Claudia Bressan, Núria Monfort, Masato Okano, Rosa Ventura","doi":"10.1002/dta.3845","DOIUrl":"https://doi.org/10.1002/dta.3845","url":null,"abstract":"<p><p>The detection of endogenous anabolic androgenic steroids misuse in Asian population using the Steroidal Module of the Athlete Biological Passport (ABP) is a challenge due to the high prevalence of UGT2B17 gene deletion polymorphism with low levels of testosterone (T) glucuronide. In this study, the capabilities of different approaches based on urine analysis for the detection of oral T undecanoate administration were evaluated in 13 Asian volunteers, including 11 subjects with del/del genotype and 2 subjects with del/ins genotype. In the first part of the work, the effect on the urinary steroid profile (SP) and on the isotope ratio mass spectrometry markers was evaluated. In this second part, the effect on endogenous sulfate markers was evaluated. Results showed that the oral T administration is detected for a much longer period of time with sulfate markers than with the conventional urinary SP markers. Androstanediol sulfate 1 (Diol-S1)/dehydroandrosterone sulfate (DHA-S) and epiandrosterone sulfate (epiA-S)/DHA-S ratios were the most diagnostic parameters for longitudinal monitoring, as reported for Caucasian volunteers in a previous work. For most subjects, sulfate markers allowed the detection of suspicious samples up to 144 h. Combinations of sulfate and glucuronide markers improved the sensitivity in comparison with the conventional SP markers, but yielded poorer results than the best sulfate ratios. Based on the results of this study and previous works, sulfate EAAS metabolites provide a consistent improvement in the detectability of T administration in both Caucasian and Asian populations. Their incorporation into the ABP should be considered.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jenny K Y Wong, Timmy L S Choi, Celia O L Wong, Peter Curl, Terence S M Wan, Emmie N M Ho
{"title":"Doping Control Analysis of Methylsulfonylmethane in Horses.","authors":"Jenny K Y Wong, Timmy L S Choi, Celia O L Wong, Peter Curl, Terence S M Wan, Emmie N M Ho","doi":"10.1002/dta.3844","DOIUrl":"https://doi.org/10.1002/dta.3844","url":null,"abstract":"<p><p>Methylsulfonylmethane (MSM), also known as dimethyl sulfone, is a naturally occurring sulphur-containing compound that can be found in plants, animals and humans. MSM can also be a metabolite of dimethyl sulfoxide (DMSO). Due to their anti-inflammatory and analgesic effects, both MSM and DMSO are prohibited substances in horseracing. As both substances are naturally occurring, their misuse in horses is controlled by International Residue Limits (IRL) of 1200 and 15 μg/mL, respectively, in horse urine as established by the International Federation of Horseracing Authorities. The elimination of DMSO in horses has been reported; however, there has been no report on the elimination of MSM in horses. This paper describes a pilot study of an administration study of MSM in two geldings following one scoop (~15 g) of Pure MSM twice daily for six consecutive days. MSM in post-administration urine and blood samples was quantified by gas chromatography-mass spectrometry after sample dilution, with additional protein precipitation for the blood samples. The elimination profiles of MSM in urine and blood are described. The maximum detection time in urine at the IRL of 1200 μg/mL was around 4.5 days after the last dose. Plasma MSM in both horses was around 120 μg/mL at 4.4 days after the last dose, which was the last blood sample collected. As such, 120 μg/mL may indicate a possible IRL for controlling MSM in horse blood. The analysis of DMSO in post-MSM-administration samples showed that DMSO is not a significant metabolite of MSM in horses.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Celine Vanhee, Maarten Dill, Michael Canfyn, Emmy Tuenter, Sophia Barhdadi
{"title":"The Emergence of a Novel Synthetic Nicotine Analog 6-Methyl Nicotine (6-MN) in Proclaimed Tobacco- and Nicotine-Free Pouches Available in Europe.","authors":"Celine Vanhee, Maarten Dill, Michael Canfyn, Emmy Tuenter, Sophia Barhdadi","doi":"10.1002/dta.3841","DOIUrl":"https://doi.org/10.1002/dta.3841","url":null,"abstract":"<p><p>A new nicotine delivery system in the form of tobacco-free nicotine pouches was introduced in Europe in 2019. These nicotine bags did not fall under the Tobacco Products Directive (TPD) II, which brought forward regulatory requirements for both cigarettes, related products, and e-liquids. As these pouches did not fall under the scope of the TPD, it was up to the member states to decide which action to be taken if any. Some EU member states banned these nicotine pouches, while others put restrictions on the amount of nicotine, warning messages, and presentation and packaging of the product, and some member states did not take any action. Likely as a result of the ban or restrictions, soon after also, tobacco and nicotine-free pouches became available in the European Union (EU). Early 2024, \"NoNIC\" pouches, claiming to be tobacco- and nicotine-free, became available on the European market. These pouches are promoted online and clearly target a younger population with a youth-appealing package design and enticing flavors. Upon analysis of different samples utilizing gas chromatography coupled to MS (GC-MS), liquid chromatography coupled to high-resolution tandem mass spectrometry (HRAM LC-MS2), and nuclear magnetic resonance spectroscopy (NMR), it was demonstrated that these pouches were indeed devoid of nicotine but contained the synthetic nicotine homolog 6-methyl nicotine (6-MN) and this up to 20 mg per pouch. Nonetheless, a part of a likely unaware/misled young adult subpopulation has easy access to these products, containing a novel molecule for which limited to no clinical effects are known.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lydia Brooks, Michael Ryan, Erin McCosham, Devan Loganathan
{"title":"Further Investigation Into an Environmental Source for Aminorex.","authors":"Lydia Brooks, Michael Ryan, Erin McCosham, Devan Loganathan","doi":"10.1002/dta.3820","DOIUrl":"https://doi.org/10.1002/dta.3820","url":null,"abstract":"<p><p>In 2009, levamisole was identified as a source for several aminorex positives reported in postrace equine samples in Canada. Since then, unexplained detections of aminorex continue to be identified in equine samples where there is no evidence to link these detections to a levamisole administration. Previous studies identified a compound named barbarin in some species of plants from the Brassicaceae family and suggested that barbarin may be a possible precursor for aminorex. The objectives of this study were to (1) investigate the link between barbarin and aminorex and (2) identify other biomarkers of plant origin. Methods were developed and validated for the detection of aminorex, barbarin, glucobarbarin, and other associated compounds. Aminorex was administered to one horse, and barbarin was not detected in any plasma and urine samples. Barbarea stricta and Barbarea orthoceras were administered to two horses, and aminorex was detected in all plasma and urine samples collected. Barbarin was detected in some plasma but not in urine samples. Resedine was observed in retrospective examination of chromatograms of the plant material and from all plants postadministration plasma and urine samples from the two horses. Resedine was administered to one horse and was detected in plasma and urine samples, but aminorex was only detected in urine samples. These results provide evidence that resedine is an intermediary compound between barbarin and aminorex in horses and that resedine can be used as a biomarker to eliminate the reporting of aminorex positives originating from the ingestion of plants from the Brassicaceae family.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HuiFen Hannah Zhang, Jia Ying Hilda Loh, Hooi Yan Moy, Chi Pang Lui
{"title":"An Improved GC-MS/MS Method for a Fast Multidrug Analysis in Hair.","authors":"HuiFen Hannah Zhang, Jia Ying Hilda Loh, Hooi Yan Moy, Chi Pang Lui","doi":"10.1002/dta.3840","DOIUrl":"https://doi.org/10.1002/dta.3840","url":null,"abstract":"<p><p>This study presents the development and validation of a drug testing method in hair, employing a semi-automated sample preparation procedure and gas chromatography-tandem mass spectrometry (GC-MS/MS) for simultaneous multidrug analysis in hair. The method aims to detect and quantify multiple drugs in hair, including amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, ketamine, norketamine, cocaine, benzoylecgonine, morphine, codeine and 6-monoacetylmorphine, using a comprehensive procedure involving decontamination, pulverization, clean-up using supported-liquid extraction (SLE) and a two-step derivatization process. The method validation included specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, carryover, robustness and stability. The results indicate a linearity range of 0.1-5 ng/mg for all drugs except methamphetamine, which has a linearity range of 0.2-5 ng/mg. The accuracy and precision of the method are within ±20%, with the LOQ at 0.2 ng/mg for methamphetamine, 0.1 ng/mg for amphetamine and MDMA and 0.05 ng/mg for the rest of the drugs. The LODs were found to be 0.1 ng/mg for methamphetamine, 0.05 ng/mg for amphetamine and MDMA and 0.025 ng/mg for other drugs. This method has demonstrated its accuracy by comparing the quantitative test results with the expected results, using hair samples from the proficiency test service providers. This test method offers efficient testing of multiple drugs in a single analysis, significantly improves the hair analysis workflow in a routine testing laboratory by reducing turnaround time and the amount of hair sample required.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}