{"title":"Simultaneous determination of diquat and its two primary metabolites in rat plasma by ultraperformance liquid chromatography-tandem mass spectrometry and its application to the toxicokinetic study.","authors":"Zhengsheng Mao, Youjia Yu, Hao Sun, Chao Wu, Qiaoyan Jiang, Chunyan Chu, Chongwen Zhao, Yujie Zhou, Jinsong Zhang, Yue Cao, Feng Chen","doi":"10.1007/s11419-022-00623-z","DOIUrl":"https://doi.org/10.1007/s11419-022-00623-z","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to develop and validate an ultraperformance liquid chromatography-tandem mass spectrometry to simultaneously determine diquat (DQ) and its two primary metabolites in rat plasma and its application to the toxicokinetic study.</p><p><strong>Method: </strong>The chromatographic separation of DQ and its two primary metabolites was performed with hydrophilic interaction chromatography column by adding formic acid and ammonium acetate in mobile phase in stepwise elution mode. DQ and its two primary metabolites were detected by liquid chromatography-tandem mass spectrometry in positive mode.</p><p><strong>Results: </strong>The lower limit of quantification ranging from 0.3 to 3.0 ng/mL for DQ and its two primary metabolites was achieved by using only 50 μL of rat plasma. The maximum concentration (C<sub>max</sub>) was 977 ng/mL, half-life (t<sub>1/2</sub>) was 13.1 h, and area under the plasma concentration-time curve (AUC<sub>0-t</sub>) was 2770 h*ng/mL for DQ, C<sub>max</sub> was 47.1 ng/mL, t<sub>1/2</sub> was 25.1 h, and AUC<sub>0-t</sub> was 180 h·ng/mL for diquat monopyridone (DQ-M) and C<sub>max</sub> was 246 ng/mL, t<sub>1/2</sub> was 8.2 h, and AUC<sub>0-t</sub> was 2430 h·ng/mL for diquat dipyridone (DQ-D), respectively.</p><p><strong>Conclusions: </strong>The validated method was shown to be suitable for simultaneous determination of diquat and its two primary metabolites in rat plasma. This study is the first to study the toxicokinetics of DQ and its two primary metabolites.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"332-339"},"PeriodicalIF":2.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9715450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9163270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kelly Francisco da Cunha, Julia Martinelli Magalhães Kahl, Taís Regina Fiorentin, Karina Diniz Oliveira, Jose Luiz Costa
{"title":"High-sensitivity method for the determination of LSD and 2-oxo-3-hydroxy-LSD in oral fluid by liquid chromatography‒tandem mass spectrometry.","authors":"Kelly Francisco da Cunha, Julia Martinelli Magalhães Kahl, Taís Regina Fiorentin, Karina Diniz Oliveira, Jose Luiz Costa","doi":"10.1007/s11419-022-00622-0","DOIUrl":"https://doi.org/10.1007/s11419-022-00622-0","url":null,"abstract":"<p><strong>Purpose: </strong>We have developed and validated a high-sensitivity method to quantify lysergic acid diethylamide (LSD) and 2-oxo-3-hydroxy-LSD (OH-LSD) in oral fluid samples using liquid-liquid extraction and liquid chromatography-tandem mass spectrometry (LC‒MS/MS). The method was applied to the quantification of both substances in 42 authentic oral fluid samples.</p><p><strong>Methods: </strong>A liquid-liquid extraction was performed using 500 µL each of samples (oral fluid samples collected using Quantisal™ device) and dichloromethane/isopropanol mixture (1:1, v/v). Enzymatic hydrolysis was evaluated to cleave glucuronide metabolites.</p><p><strong>Results: </strong>The limit of quantification was 0.01 ng/mL for both LSD and OH-LSD. The linearity was assessed between 0.01 and 5 ng/mL. Imprecision and bias were not higher than 10.2% for both analytes. Extraction recovery was higher than 69%. The analytes were stable in the autosampler at 10 °C for 24 h, and up to 30 days at 4 and -20 °C. The method was applied to the analysis of 42 oral fluid samples. LSD was detected in all samples (concentrations between 0.02 and 175 ng/mL), and OH-LSD was detected in 20 samples (concentrations between 0.01 and 1.53 ng/mL).</p><p><strong>Conclusions: </strong>A high-sensitive method was fully validated and applied to authentic samples. To our knowledge, this is the first work to report concentrations of LSD and OH-LSD in authentic oral fluid samples.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"322-331"},"PeriodicalIF":2.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9163268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kieran R Manchester, Laura Waters, Shozeb Haider, Peter D Maskell
{"title":"The blood-to-plasma ratio and predicted GABA<sub>A</sub>-binding affinity of designer benzodiazepines.","authors":"Kieran R Manchester, Laura Waters, Shozeb Haider, Peter D Maskell","doi":"10.1007/s11419-022-00616-y","DOIUrl":"https://doi.org/10.1007/s11419-022-00616-y","url":null,"abstract":"<p><strong>Purpose: </strong>The number of benzodiazepines appearing as new psychoactive substances (NPS) is continually increasing. Information about the pharmacological parameters of these compounds is required to fully understand their potential effects and harms. One parameter that has yet to be described is the blood-to-plasma ratio. Knowledge of the pharmacodynamics of designer benzodiazepines is also important, and the use of quantitative structure-activity relationship (QSAR) modelling provides a fast and inexpensive method of predicting binding affinity to the GABA<sub>A</sub> receptor.</p><p><strong>Methods: </strong>In this work, the blood-to-plasma ratios for six designer benzodiazepines (deschloroetizolam, diclazepam, etizolam, meclonazepam, phenazepam, and pyrazolam) were determined. A previously developed QSAR model was used to predict the binding affinity of nine designer benzodiazepines that have recently appeared.</p><p><strong>Results: </strong>Blood-to-plasma values ranged from 0.57 for phenazepam to 1.18 to pyrazolam. Four designer benzodiazepines appearing since 2017 (fluclotizolam, difludiazepam, flualprazolam, and clobromazolam) had predicted binding affinities to the GABA<sub>A</sub> receptor that were greater than previously predicted binding affinities for other designer benzodiazepines.</p><p><strong>Conclusions: </strong>This work highlights the diverse nature of the designer benzodiazepines and adds to our understanding of their pharmacology. The greater predicted binding affinities are a potential indication of the increasing potency of designer benzodiazepines appearing on the illicit drugs market.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"349-356"},"PeriodicalIF":2.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9715504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9180144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Quantification of MDMB-4en-PINACA and ADB-BUTINACA in human hair by gas chromatography-tandem mass spectrometry.","authors":"Yue Wang, Yefei Pan, Hongkun Yang, Jinlei Liu, Amin Wurita, Koutaro Hasegawa","doi":"10.1007/s11419-022-00615-z","DOIUrl":"https://doi.org/10.1007/s11419-022-00615-z","url":null,"abstract":"<p><strong>Purpose: </strong>To test synthetic cannabinoid (SCs) in parent forms from living human, the hairs seems to be one of the best samples, because of the non-invasiveness upon their collection. The purpose of this study is to establish a method for quantification of MDMB-4en-PINACA and ADB-BUTINACA, the most recently abused SCs in hair samples, using gas chromatography-tandem mass spectrometry (GC-MS/MS).</p><p><strong>Methods: </strong>The collected hair samples were washed with a detergent solution, following by water and acetone. After drying cutting them into about 2 mm sections, they were ground by a cryogenic grinder into powder. The 50-mg powder with internal standard(s) plus 1 mL methanol were vortexed, and centrifuged to obtain the supernatant layer. After its evaporation and reconstitution with 50 µL methanol, 1-µL aliquot of it was subjected to analysis.</p><p><strong>Results: </strong>The standard calibration curves were created for both MDMB-4en-PINACA and ADB-BUTINACA in blank hair samples; good linear curves were obtained in the range of 20-20,000 pg/mg with correlation coefficients greater than 0.99. The limits of detection and limits of quantification were 10 and 20 pg/mg, respectively. Other validation parameters were all satisfactory. The concentrations of MDMB-4en-PINACA obtained from 3 authentic subjects and ADB-BUTINACA obtained from 3 authentic subjects were 26.2-806 pg/mg and 63.1-430 pg/mg, respectively.</p><p><strong>Conclusions: </strong>In the present article, the details of simple and rapid quantification of MDMB-4en-PINACA and ADB-BUTINACA in human scalp hair have been established. To our knowledge, this is the first report for quantification of SCs in hair samples by GC-MS/MS.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"340-348"},"PeriodicalIF":2.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9163266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiao-Jiao Ji, Junbo Zhao, Ping Xiang, Hui Yan, Min Shen
{"title":"Chiral analysis of dextromethorphan and levomethorphan in human hair by liquid chromatography-tandem mass spectrometry.","authors":"Jiao-Jiao Ji, Junbo Zhao, Ping Xiang, Hui Yan, Min Shen","doi":"10.1007/s11419-022-00620-2","DOIUrl":"https://doi.org/10.1007/s11419-022-00620-2","url":null,"abstract":"<p><strong>Purpose: </strong>Methorphan exists in two enantiomeric forms including dextromethorphan and levomethorphan. Dextromethorphan is an over-the-counter antitussive drug, whereas levomethorphan is strictly controlled as a narcotic drug. Chiral analysis of methorphan could, therefore, assist clinicians and forensic experts in differentiating between illicit and therapeutic use and in tracing the source of the drug.</p><p><strong>Methods: </strong>A method for enantiomeric separation and quantification of levomethorphan and dextromethorphan in human hair was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Hair was extracted in hydrochloric acid/methanol (1:20, v/v). The supernatant were separated using a Supelco Astec Chirobiotic™ V2 column (250 × 2.1 mm, i.d., 5 μm particle size) and analyzed on a triple quadrupole linear ion trap mass spectrometer in multiple reaction monitoring mode.</p><p><strong>Results: </strong>The limits of detection for dextromethorphan and levomethorphan were 2 and 1 pg/mg, respectively; the lower limit of quantification was 2 pg/mg for both drugs. Good linearity (r > 0.995) was observed for both analytes over the linear range. Precision values were below 10% for both analytes; accuracy values ranged from 87.5 to 101%. The extraction recoveries were 78.3-98.4%, and matrix effects were 70.5-88.6%. This method was applied to human hair samples from 120 people suspected of methorphan use to further distinguish the drug chirality. Dextromethorphan was detected in all 120 samples at a concentration range of 2.7-19,100 pg/mg, whereas levomethorphan was not detected in any sample.</p><p><strong>Conclusions: </strong>A sensitive quantitative method was established for the enantiomeric separation of dextromethorphan and levomethorphan in hair. This is the first study to achieve chiral analysis of methorphan in human hair.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"312-321"},"PeriodicalIF":2.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9163267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Duoqi Xu, Jiaojiao Ji, Ping Xiang, Hui Yan, Min Shen
{"title":"Two DFSA cases involving midazolam clarified by the micro-segmental hair analyses.","authors":"Duoqi Xu, Jiaojiao Ji, Ping Xiang, Hui Yan, Min Shen","doi":"10.1007/s11419-022-00621-1","DOIUrl":"https://doi.org/10.1007/s11419-022-00621-1","url":null,"abstract":"<p><strong>Purpose: </strong>In this study, an analytical procedure to identify trace amounts of drug in hair based on micro-segmental hair analysis was presented. The method also can be used to estimate the time of drug ingestion at daily precision by cutting a single hair into sub-millimeter segments which correspond to daily hair growth.</p><p><strong>Methods: </strong>A method was established for efficient extraction of midazolam, one of the most frequently detected compound in drug-facilitated sexual assault (DFSA) cases, from each 0.4-mm hair segment and validated by ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Moreover, two DFSA cases were used to compare the micro-segmental hair analysis with the 1- cm segmental analysis method.</p><p><strong>Results: </strong>The validation showed a lower limit of quantification of 0.5 pg/mm for midazolam, with intraday and interday accuracies (bias) from - 5.2 to 0.9%. The micro-segmental hair analysis method was applied to proximal 1-cm hair segment including hair bulbs in two DFSA cases. The micro-segmental hair analysis results in case 1 showed midazolam in the S15-S17 (5.6-6.8 mm from hair bulb) in a concentration range from 0.5 to 0.9 pg/mm, and the concentrations of midazolam in all hair micro-segments (0-1 cm from the scalp) in case 2 were from 0.5 to 2.0 pg/mm.</p><p><strong>Conclusions: </strong>Comparison with the conventional method revealed that micro-segmental hair analysis may enhance the utility of hair drug testing and strengthen probative force in DFSA cases.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"374-382"},"PeriodicalIF":2.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9163269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Determination of cyanide in blood by GC-MS using a new high selectivity derivatization reagent 1,2,3,3-tetramethyl-3H-indolium iodide.","authors":"Yasuhiro Morikawa, Keiji Nishiwaki, Shigeo Suzuki, Kazutaka Shiomi, Isao Nakanishi","doi":"10.1007/s11419-021-00610-w","DOIUrl":"https://doi.org/10.1007/s11419-021-00610-w","url":null,"abstract":"","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"393-399"},"PeriodicalIF":2.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9180138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Forensic ToxicologyPub Date : 2022-07-01Epub Date: 2022-01-04DOI: 10.1007/s11419-021-00611-9
Koji Yamaguchi, Hajime Miyaguchi, Youkichi Ohno, Yoshimasa Kanawaku
{"title":"Qualitative analysis of 7- and 8-hydroxyzolpidem and discovery of novel zolpidem metabolites in postmortem urine using liquid chromatography-tandem mass spectrometry.","authors":"Koji Yamaguchi, Hajime Miyaguchi, Youkichi Ohno, Yoshimasa Kanawaku","doi":"10.1007/s11419-021-00611-9","DOIUrl":"10.1007/s11419-021-00611-9","url":null,"abstract":"<p><strong>Purpose: </strong>Zolpidem (ZOL) is a hypnotic sometimes used in drug-facilitated crimes. Understanding ZOL metabolism is important for proving ZOL intake. In this study, we synthesized standards of hydroxyzolpidems with a hydroxy group attached to the pyridine ring and analyzed them to prove their presence in postmortem urine. We also searched for novel ZOL metabolites in the urine sample using liquid chromatography-triple quadrupole mass spectrometry (LC-QqQMS) and liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QqTOFMS).</p><p><strong>Methods: </strong>7- and 8-Hydroxyzolpidem (7OHZ and 8OHZ, respectively) were synthesized and analyzed using LC-QqQMS. Retention times were compared between the synthetic standards and extracts of postmortem urine. To search for novel ZOL metabolites, first, the urine extract was analyzed with data-dependent acquisition, and the peaks showing the characteristic fragmentation pattern of ZOL were selected. Second, product ion spectra of these peaks at various collision energies were acquired and fragments that could be used for multiple reaction monitoring (MRM) were chosen. Finally, MRM parameters were optimized using the urine extract. These peaks were also analyzed using LC-QqTOFMS.</p><p><strong>Results: </strong>The presence of 7OHZ and 8OHZ in urine was confirmed. The highest peak among hydroxyzolpidems was assigned to 7OHZ. The novel metabolites found were zolpidem dihydrodiol and its glucuronides, cysteine adducts of ZOL and dihydro(hydroxy)zolpidem, and glucuronides of hydroxyzolpidems.</p><p><strong>Conclusions: </strong>The presence of novel metabolites revealed new metabolic pathways, which involve formation of an epoxide on the pyridine ring as an intermediate.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"263-277"},"PeriodicalIF":2.8,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9715527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9180139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sabrina Büttenbender, Graciela Carlos, Martin Steppe, Rafael Scorsatto Ortiz, Renata Pereira Limberger, Andreas Sebastian Loureiro Mendez
{"title":"Fast and reliable profiling of cannabinoids in seized samples using the method of HPLC-DAD followed by chemometrics.","authors":"Sabrina Büttenbender, Graciela Carlos, Martin Steppe, Rafael Scorsatto Ortiz, Renata Pereira Limberger, Andreas Sebastian Loureiro Mendez","doi":"10.1007/s11419-022-00625-x","DOIUrl":"https://doi.org/10.1007/s11419-022-00625-x","url":null,"abstract":"","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"407-413"},"PeriodicalIF":2.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10665235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Quantitation of sibutramine in human hair using gas chromatography-isotope dilution tandem mass spectrometry.","authors":"Hongkun Yang, Amin Wurita, Jinlei Liu, Yue Wang, Koutaro Hasegawa","doi":"10.1007/s11419-021-00609-3","DOIUrl":"https://doi.org/10.1007/s11419-021-00609-3","url":null,"abstract":"<p><strong>Purpose: </strong>An analytical method for quantitation of sibutramine in human hair using gas chromatography (GC)-isotope dilution tandem mass spectrometry (MS/MS) was newly established. In this article, a case is presented, in which a 3.5-year-old male child accidentally ingested chocolate-like product containing sibutramine, showing various symptoms; he could survived the crisis. About 1 month after the incident, his scalp hair sample was subjected to analysis for the causative sibutramine.</p><p><strong>Method: </strong>After cryo-grinding for the hair sample, target compound was extracted with methanol, and the solvent layer was evaporated to dryness. The residue was reconstituted in methanol and analyzed by GC-MS/MS, using the selected reaction monitoring (SRM) mode with a deuterated isotope internal standard.</p><p><strong>Results: </strong>The substance was identified as sibutramine; its concentration in the hair sample of the child was 58.6 pg/mg. The calibration curve of sibutramine in hair samples had a good linear relationship in the concentration range of 20-200 pg/mg (r > 0.99); the extraction recovery rate 85.2-91.8%; the interday and intraday precision and accuracy (bias) examined not greater than 9.6%. Sibutramine in human hair had good stability under 3 different storage conditions at room (20 °C), refrigerated (4 °C) and frozen ( - 20 °C) temperatures for at least 7 days.</p><p><strong>Conclusions: </strong>It should be expected that the method established in this study would contribute to rapid determinations of sibutramine. To our knowledge, this is the first report describing quantitation of sibutramine in an authentic human hair sample by GC-MS/MS.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"366-373"},"PeriodicalIF":2.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10612049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}