Biomedical Chromatography最新文献

{"title":"Method validation, residue behaviour and dietary risk assessment of insecticides (cyantraniliprole, acetamiprid, flubendiamide and its metabolite, des-iodo flubendiamide) in or on broccoli using LC–MS/MS","authors":"Sakshi Sharma,&nbsp;Sapna Katna,&nbsp;Ajay Sharma,&nbsp;Pankaj Sharma Istatu,&nbsp;Nisha Devi,&nbsp;Arvind Kumar,&nbsp;Shubhra Singh","doi":"10.1002/bmc.5962","DOIUrl":"10.1002/bmc.5962","url":null,"abstract":"<p>Residue behaviour and dietary risk assessment of cyantraniliprole, flubendiamide and acetamiprid in broccoli were carried out using the QuEChERS (quick, easy, cheap, effective, rugged and safe) technique coupled with LC–MS/MS. The QuEChERS technique was validated on parameters such as linearity, accuracy, precision, robustness, matrix effects, limit of quantification (LOQ), specificity, retention time and ion ratio as per SANTE (Directorate General for Health and Food Safety) guidelines to attest to the specificity, accuracy and precision of the analytical method in estimating insecticide residues in and on broccoli heads and cropped soil. The LOQ of the method for all three insecticides was 0.01 mg/kg. The initial deposits of cyantraniliprole, flubendiamide and acetamiprid reduced to half of its concentration in 1.873–2.354, 1.975–2.484 and 1.371–1.620 days, respectively. No residues were detected in broccoli-cropped soil at harvest time (30 days after last spray). The proposed maximum residue limits (MRLs) of 1.5, 0.5–0.9 and 2.0–3 mg/kg for cyantraniliprole, flubendiamide and acetamiprid were calculated using the Organisation for Economic Co-operation and Development MRL calculator. The acute and chronic dietary risk assessment of the tested insecticides identified no appreciable dietary risk to the Indian population from the consumption of broccoli heads. The findings of no dietary risk highlight the importance of informed pesticide usage in broccoli and the proposed MRL derived from this study offers crucial guidelines for the regulatory authorities, ensuring the safety of broccoli consumption.</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"38 10","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625869","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":"Analysis of blood concentrations and clinical application of risdiplam in patients with spinal muscular atrophy using ultra-high performance liquid chromatography–tandem mass spectrometry","authors":"Xian Wu,&nbsp;Zhiyan Lin,&nbsp;Yan Liu,&nbsp;Xinzhu Liu,&nbsp;Zhenghong Yi,&nbsp;Xiaohui Huang,&nbsp;Jian Zhang","doi":"10.1002/bmc.5934","DOIUrl":"10.1002/bmc.5934","url":null,"abstract":"<p>Risdiplam, the first oral therapy approved for spinal muscular atrophy and made globally available in 2021, necessitates a highly sensitive and straightforward assay for therapeutic drug monitoring. This is crucial to manage potential toxicities linked to drug concentrations and supervise dosing regimens. A cutting-edge ultra-high performance liquid chromatography–tandem mass spectrometry bioassay for risdiplam in human serum has been developed. In this method, analytes were separated on a Phenomenex Kinetex XB C₁₈ column using a 6.5-min gradient elution after a single-step protein precipitation. MS detection was conducted via electrospray ionization in positive mode with selected reaction monitoring. The validated range for risdiplam was determined to be 1.95–125.00 ng/mL. The precision and accuracy of intra- and inter-batch analyses were within ±15%. The novel method met all other established criteria. This assay holds promise for monitoring drug concentrations and guiding clinical decisions in patients with spinal muscular atrophy.</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"38 10","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619215","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":"A validated stability-indicating reversed-phase-UPLC method for simultaneous estimation of promethazine hydrochloride, methylparaben, propylparaben and sodium benzoate assay of cough suppressant and antihistamine liquid oral dosage forms","authors":"Sreenivas Pippalla,&nbsp;Arjuna Rao Nekkalapudi,&nbsp;Venugopal Reddy Komreddy","doi":"10.1002/bmc.5944","DOIUrl":"10.1002/bmc.5944","url":null,"abstract":"<p>A quick, simple, sensitive, efficient and stability-indicating reverse-phase ultraperformance liquid chromatographic method for the estimation of propylparaben, methylparaben and sodium benzoate in a pharmaceutical liquid oral formulation was developed. A Waters Acquity UPLC BEH C₁₈, 50 × 2.1 mm, 1.7 μm i.d. column was used to perform chromatographic separation with a 0.1% perchloric acid mobile phase used as solvent A and a mixture of 0.1 % perchloric acid and methanol in the ratio 20:80 (v/v), respectively, as solvent B. The experiments were carried out at a flow rate of 0.4 ml/min and the detection wavelength was 240 nm. The compartment temperature of the column was set at 40°C and the injection volume was set at 2 μl. The main aim of the research was to develop a single UPLC assay method for promethazine (active ingredient) and preservatives in the oral solution of promethazine HCl and dextromethorphan HBr that contains promethazine (active ingredient) and methylparaben, propylparaben and sodium benzoate (preservatives). An assay of dextromethorphan HBr was developed and validated by another HPLC method. The drug and preservatives were eluted at retention times of 19.3 min for promethazine HCl, 9.3 min for methylparaben, 18.9 min for propylparaben and 8.9 min for sodium benzoate. Validation of the developed method was carried out as stated by the International Conference on Harmonization guidelines ICH Q2B and under USP&lt;1225&gt;. The analytical parameters verified specificity/selectivity, linearity, accuracy, ruggedness and robustness. The linearity ranges of promethazine HCL, methylparaben, propylparaben and sodium benzoate were 10–100, 10–80, 1.0–8.0 and 10–80 μg/ml, respectively, with a correlation coefficient of active ingredients and preservatives of 1.00. Percentage recoveries of promethazine, propylparaben, methylparaben, and sodium benzoate were 100.0–100.2, 99.0–100.3, 99.5–98.0 and 99.0–100.0%. The validated analytical method proves that the method is specific, precise, linear, accurate, sensitive, rugged and stable, indicating the quantification of the active ingredient and all preservatives in liquid oral formulations.</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"38 9","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615876","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":"In vivo and in vitro chemical composition and biological activity of traditional vs. dispensing granule decoctions of Coptidis Rhizoma: A comparative study","authors":"Panpan Wang,&nbsp;Xinjing Gui,&nbsp;Manwen Xu,&nbsp;Fengyu Dong,&nbsp;Yuanyuan Li,&nbsp;Qi Wang,&nbsp;Yanli Wang,&nbsp;Jing Yao,&nbsp;Lu Lu,&nbsp;Ruixin Liu","doi":"10.1002/bmc.5960","DOIUrl":"10.1002/bmc.5960","url":null,"abstract":"<p>Coptidis Rhizoma (CR) holds significant clinical importance. In this study, we conducted a comparative analysis of CR's dispensing granule decoction (DGD) and traditional decoction (TD) to establish a comprehensive evaluation method for the quality of DGD. We selected nine batches of DGD (three from each of manufacturers A, B and C) and 10 batches of decoction pieces for analysis. We determined the content of representative components using high-performance liquid chromatography and assessed the content of blood components <i>in vivo</i> post-administration using ultra-performance liquid chromatography–mass spectrometry. The antibacterial activity was measured using the drug-sensitive tablet method. To evaluate the overall consistency of DGD and TD, we employed the CRITIC method and Grey relational analysis method. Our CRITIC results indicated no significant difference between the CRITIC scores of DGD-B and TD, with DGD-B exhibiting the highest consistency and overall quality. However, DGD-A and DGD-C showed variations in CRITIC scores compared with TD. After equivalent correction, the quality of DGD-A and DGD-C approached that of TD. Furthermore, our Grey relational analysis results supported the findings of the CRITIC method. This study offers a novel approach to evaluate the consistency between DGD and TD, providing insights into improving the quality of DGD.</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"38 9","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589468","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":"Integrating metabolomics and bioinformatics to reveal the mechanism of Epimedium-induced liver injury","authors":"Jiaqi Wang,&nbsp;Yijia Cao,&nbsp;Mo Sun,&nbsp;Tonghua Zhang,&nbsp;Gengyuan Yu,&nbsp;Haoran Xu,&nbsp;Tianyi Li,&nbsp;Chenning Zhang,&nbsp;Yikun Sun","doi":"10.1002/bmc.5948","DOIUrl":"10.1002/bmc.5948","url":null,"abstract":"<p>Epimedium is a traditional Chinese medicine with a wide range of clinical applications; however, there have been numerous reports of adverse reactions in recent years. The most common side effect of Epimedium is liver injury. In this study, the liquid chromatography–mass spectrometry (LC–MS) method has been established to study the components of Epimedium and to identify the components absorbed into the blood of rats. Bioinformatics was used to screen out potential toxic components, and the integrating metabolomics method was used to explore the molecular mechanism of Epimedium-induced liver injury. The chemical constituents of Epimedium were identified by LC–MS, and 62 compounds were obtained, including 57 flavonoids, four organic acids and one alkaloid. The toxicity network of “Epimedium–component–target–liver injury” was constructed using bioinformatics research methods, and then the key hepatotoxic component icaritin was identified. Integrating metabolomics was used to investigate the changes in the metabolic profile of L-02 cells with different durations of icaritin administration compared with the control group, and 106 different metabolites were obtained. A total of 14 potential biomarkers significantly associated with cell survival were screened by Pearson correlation analysis combined with the L-02 cell survival rate. Our study preliminarily revealed the mechanism of hepatotoxicity induced by Epimedium.</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"38 9","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562576","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":"Spectrum–effect relationship between HPLC fingerprint and hypoglycemic of litchi leaves (Litchi chinensis Sonn) in vitro","authors":"Yanli Liang,&nbsp;Jingjing Xie,&nbsp;Dongfang Huang,&nbsp;Yupin Cao,&nbsp;Piaoxue Zheng,&nbsp;Chunlian Lu,&nbsp;Yuming Ma,&nbsp;Jiawen Peng,&nbsp;Zujie Qin,&nbsp;Jie Liang","doi":"10.1002/bmc.5950","DOIUrl":"10.1002/bmc.5950","url":null,"abstract":"<p><i>Litchi chinensis</i> Sonn (Litchi) has been listed in the <i>Chinese Pharmacopeia</i>, and is an economically and medicinally valuable species within the family Sapindaceae. However, the material basis of its pharmacological action and the pharmacodynamic substances associated with its hypoglycemic effect are still unclear. The predominant objective of this study was to establish the fingerprint profile of litchi leaves and to evaluate the relationship between the components of the high-performance liquid chromatography (HPLC) fingerprint of litchi leaves, assess its hypoglycemic effect by measuring <i>α</i>-glucosidase and <i>α</i>-amylase inhibition, and find the spectrum–effect relationship of litchi leaves by bivariate correlation analysis, Grey relational analysis and partial least squares regression analysis. In this study, the fingerprint of litchi leaves was established by HPLC, and a total of 15 common peaks were identified that clearly calibrated eight components, with P1 being gallic acid, P2 being protocatechuic acid, P3 being catechin, P6 being epicatechin, P12 being rutin, P13 being astragalin, P14 being quercetin and P15 being kaempferol. The similarities between the fingerprints of 11 batches of litchi leaves were 0.766–0.979. Simultaneously, the results of the spectrum–effect relationship showed that the chemical constituents represented by peaks P8, P3, P12, P14, P2, P13, and P11 were relevant to the hypoglycemic effect.</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"38 9","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554151","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":"Screening of inhibitors on successful covalent tyrosinase coupling with help from SpyBank","authors":"Yu Yi,&nbsp;Xuewang Gong,&nbsp;Mengyuan Cui,&nbsp;Yuting Liang,&nbsp;Jianfeng Mei,&nbsp;Guoqing Ying,&nbsp;Yinfei Wu","doi":"10.1002/bmc.5957","DOIUrl":"10.1002/bmc.5957","url":null,"abstract":"<p>Microbial metabolites are an important source of tyrosinase (TYR) inhibitors because of their rich chemical diversity. However, because of the complex metabolic environment of microbial products, it is difficult to rapidly locate and identify natural TYR inhibitors. Affinity-based ligand screening is an important method for capturing active ingredients in complex samples, but ligand immobilization is an important factor affecting the screening process. In this paper, TYR was used as ligand, and the SpyTag/SpyCatcher coupling system was used to rapidly construct affinity chromatography vectors for screening TYR inhibitors and separating active components from complex samples. We successfully expressed SpyTag–TYR fusion protein and SpyCatcher protein, and incubated SpyCatcher protein with epoxy-activated agarose. The SpyTag–TYR protein was spontaneously coupled with SpyCatcher to obtain an affinity chromatography filler for immobilization of TYR, and the performance of the packaging material was characterized. Finally, compound 1 with enzyme inhibitory activity was successfully obtained from the fermentation product of marine microorganism C. Through HPLC, MS, ¹H NMR and ¹³C NMR analyses, its structure was deduced as azelaic acid, and its activity was analyzed. The results showed that this is a feasible method for screening TYR inhibitors in complex systems.</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"38 9","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554150","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":"An analytical method using salting-out assisted liquid–liquid extraction to quantify ceftriaxone from micro volumes of human serum","authors":"Yuji Mukai,&nbsp;Narushi Sugii,&nbsp;Kosuke Doki,&nbsp;Masato Homma","doi":"10.1002/bmc.5955","DOIUrl":"10.1002/bmc.5955","url":null,"abstract":"<p>Ceftriaxone (CTRX) is a commonly used cephalosporin antibiotic. It is suggested that monitoring plasma/serum concentrations is helpful for its safe use. This study aimed to develop and validate an analytical method for measuring CTRX concentrations in human serum according to International Conference on Harmonization guideline M10. Ten microliters of serum sample was purified using a salting-out assisted liquid–liquid extraction procedure with magnesium sulfate. The upper layer was then diluted threefold and analyzed using a liquid chromatography–tandem mass spectrometry-based method with a total run time of 12 min. The linear calibration curve was obtained over the concentration range 5–500 μg/ml. The within-run accuracy varied from 0.2 to 6.5%, and the precision was ≤8.0%. The between-run accuracy and precision ranged from 0.7% to 5.6% and ≤6.4%, respectively. Significant carryover was resolved by injecting four blanks after high-concentration CTRX samples. The recovery rates from spiked serum at low and high concentrations were 44.4 and 43.4%, respectively. Other factors, including selectivity, matrix effects, stability, dilution integrity and reinjection reproducibility also met the acceptance criteria. Serum concentrations in 14 samples obtained from two participants receiving 2 g/day of CTRX were successfully determined using this method.</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"38 9","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554115","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":"Plasma metabolites and inflammatory proteins profiling predict outcome of Fufang Duzhong Jiangu granules treating Kashin–Beck disease","authors":"Xingxing Deng,&nbsp;Hui Niu,&nbsp;Qian Zhang,&nbsp;Jinfeng Wen,&nbsp;Yijun Zhao,&nbsp;Gaowa Naren,&nbsp;Huan Liu,&nbsp;Xiong Guo,&nbsp;Feng Zhang,&nbsp;Cuiyan Wu","doi":"10.1002/bmc.5945","DOIUrl":"10.1002/bmc.5945","url":null,"abstract":"<p>To investigate predictive biomarkers that could be used to identify patients’ response to treatment, plasma metabolomics and proteomics analyses were performed in Kashin–Beck disease (KBD) patients treated with Fufang Duzhong Jiangu Granules (FDJG). Plasma was collected from 12 KBD patients before treatment and 1 month after FDJG treatment. LC–MS and olink proteomics were employed for obtaining plasma metabolomics profiling and inflammatory protein profiles. Patients were classified into responders and non-responders based on drug efficacy. Enrichment analyses of differential metabolites and proteins of the responders at baseline and after treatment were conducted to study the mechanism of drug action. Differential metabolites and proteins between the two groups were screened as biomarkers to predict the drug efficacy. The receiver operating characteristic curve was used to evaluate the prediction accuracy of biomarkers. The changes in metabolites and inflammatory proteins in responders after treatment reflected the mechanism of FDJG treatment for KBD, which may act on glycerophospholipid metabolism, <span>d</span>-glutamine and <span>d</span>-glutamate metabolism, nitrogen metabolism and NF-kappa B signaling pathway. Three metabolites were identified as potential predictors: <i>N</i>-undecanoylglycine, <i>β</i>-aminopropionitrile and PC [18:3(6<i>Z</i>,9<i>Z</i>,12<i>Z</i>)/20:4(8<i>Z</i>,11<i>Z</i>,14<i>Z</i>,17<i>Z</i>)]. For inflammatory protein, interleukin-8 was identified as a predictive biomarker to detect responders. Combined use of these four biomarkers had high predictive ability (area under the curve = 0.972).</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"38 9","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554116","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":"Investigating the detection of the novel doping-relevant peptide kisspeptin-10 in urine using liquid chromatography high-resolution mass spectrometry","authors":"Thibo Colpaert,&nbsp;Martijn Risseeuw,&nbsp;Koen Deventer,&nbsp;Peter Van Eenoo","doi":"10.1002/bmc.5946","DOIUrl":"10.1002/bmc.5946","url":null,"abstract":"<p>Kisspeptin-10 is a peptide hormone capable of increasing circulating follicle-stimulating hormone, luteinizing hormone and testosterone levels in humans. Clinically, these effects suggest its use as a treatment for infertility. However, its testosterone-increasing effect indicates potential misuse in sports. As such, it is included in the 2024 World Anti-Doping Agency Prohibited List. This work describes the successful validation of an initial testing procedure (screening) and a confirmation procedure for kisspeptin-10 in urine using liquid chromatography–mass spectrometry. Additionally, kisspeptin-10 was incubated in human serum to mimic endogenous metabolism to improve method sensitivity, as previous research had demonstrated a rapid elimination time of only 30 min after injection (in rats). Four metabolites, corresponding to peptide fragments y9, y8, y7 and y5, were found and added to the ITP in full scan mode. A degradation product discovered during early experimentation was found to probably be caused by oxidation of the tryptophan residue into a kynurenine residue. Further research should elucidate the kinetic parameters of the reaction to improve product stability. Using the validated confirmation procedure, a black-market vial of kisspeptin-10 was analysed. The product contained no unexpected impurities, although it appeared to have undergone more degradation than the purchased reference standard.</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"38 9","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557946","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}