Pharmazie最新文献

{"title":"Adverse events associated with mesalazine in the real-world: A comprehensive pharmacovigilance analysis of the FAERS and JADER databases.","authors":"Shiyi Zhou, Yao Cheng, Yan Qian, Qingqing DU","doi":"10.1691/ph.2025.5549","DOIUrl":"10.1691/ph.2025.5549","url":null,"abstract":"<p><p><i>Objective:</i> We conducted a pharmacovigilance analysis of mesalazine-related adverse events (AEs) in the realworld using the America's FAERS and Japan's JADER databases. <i>Methods:</i> We extracted reports of mesalazine-associated AEs from FAERS and JADER spanning the first quarter of 2004 to the third quarter of 2024. In the disproportionality analysis, we applied the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma-Poisson shrinker (MGPS) algorithms for signal detection. The time to onset of AEs was assessed using Kaplan-Meier curves and the Weibull distribution test. <i>Results:</i> The analysis encompassed 40,265 AEs reports from FAERS and 4,330 from JADER. Mesalazine-related preferred terms (PTs) mapped to 27 System Organ Classes (SOCs) in FAERS and 25 SOCs in JADER. Gastrointestinal disorders emerged as the most frequently reported SOC in both databases. Three SOCs demonstrated significant signal strength across both datasets: (1) gastrointestinal disorders, (2) general disorders and administration site conditions, and (3) respiratory, thoracic, and mediastinal disorders. Common AEs including diarrhœa, pancreatitis, gastroenteritis, asmyopericarditis, proctitis ulcerative, and glutamate dehydrogenase level abnormal aligned with established drug labeling. Notably, novel pharmacovigilance signals were detected for organizing pneumonia (FAERS: n = 113, ROR = 35.21, 95%CI 29.21-42.46; JADER: n = 32, ROR = 7.90, 5.56-11.22) and eosinophilic pneumonia (FAERS: n = 77, ROR = 41.25, 32.87-51.76; JADER: n = 179, ROR = 57.69, 49.26-67.56), both requiring urgent clinical attention. AEs mainly occurred within 30 days (58.36%) with a median onset of 17 days, and the median onset time of female patients (12 days) was shorter than male patients (25 days). <i>Conclusion:</i> This pharmacovigilance study provides clinically significant evidence regarding safety-associated adverse events (AEs) of mesalazine in real-world settings. The detection of novel safety signals, particularly organizing pneumonia and eosinophilic pneumonia, highlights the necessity for enhanced post-marketing surveillance through longitudinal AE monitoring. Our findings contribute to the evolving safety profile of mesalazine and warrant further clinical investigations to validate their clinical relevance and establish causal relationships.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":"80 4","pages":"60-69"},"PeriodicalIF":1.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855917","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":"Formulation development and optimization of artemether-lumefantrine self-nanoemulsifying drug delivery systems.","authors":"T R Mudyahoto, O A Omoteso, S M Khamanga, R B Walker","doi":"10.1691/ph.2025.5008","DOIUrl":"10.1691/ph.2025.5008","url":null,"abstract":"<p><p>Poor aqueous solubility may decrease the absorption and oral bioavailability of lipophilic drugs. In the current study, artemether (ART) and lumefantrine (LMF) o/w self-nano emulsifying drug delivery system (SNEDDS) formulations were prepared. Equilibrium solubility studies were conducted and pseudo-ternary phase diagrams were constructed to identify excipients with the best solubilizing capacity for ART and LMF. They were subsequently used to manufacture and optimize SNEDDS using experimental designs, which were then characterized. Solubility and emulsification studies revealed that ART and LMF are highly soluble in oleic acid (OA). Cremophor^® EL (CEL) and Transcutol^® HP (THP) were selected as surfactant and co-surfactant. The addition of Capryol™ 90 (C90) increased the region of nano-emulsion formation without evidence of precipitation of ART and LMF. Compatibility studies revealed no prominent or significant incompatibilities between the drugs and selected excipients. The optimized formulation was stable as dispersions with nano-sized droplets and a loading capacity >99 % for both ART and LMF and a release >95% within 15 min for both drugs, reflecting a significant increase in the rate and extent of dissolution compared to that of the pure drug.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":"80 4","pages":"39-50"},"PeriodicalIF":1.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855919","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":"Glycyrrhizic acid inhibited inflammatory response in LPS-stimulated microglial BV2 cells via MAPK, Akt and NF-κB signaling pathways.","authors":"Binfeng Cheng, Yuqian Dong, Xiaolu Li, Haoheng Yu, Yu Feng, Yilong Wang, Yaxin Liu, Chen Liu, Lei Wang","doi":"10.1691/ph.2025.5532","DOIUrl":"10.1691/ph.2025.5532","url":null,"abstract":"<p><p>Activation of microglia plays a pivotal role in the pathogenesis of neuroinflammation-mediated neurodegenerative diseases. Glycyrrhizic acid (GA), a principal triterpenoid saponin in <i>Glycyrrhiza glabra</i>, has been reported to exhibit a range of biological activities. Nevertheless, the function of GA in microglia activation remains unclear. In this study, the effects and mechanisms of GA on the inflammatory response were investigated in the lipopolysaccharides (LPS)-stimulated microglial BV2 cells. BV2 cells were treated with GA (0, 20 and 50 μM), followed by stimulation with LPS (1 μg/mL). The results demonstrated that GA significantly inhibited the expression of tumor necrosis factor-α (TNF-α ) and interleukin-1β (IL-1β) at the mRNA and protein levels induced by LPS. Furthermore, the release of reactive oxygen species (ROS) and the migration of microglia were suppressed by GA in LPS-stimulated BV2 cells. In addition, GA reduced the activation of mitogen-activated protein kinases (MAPKs) and the phosphorylation of Akt. GA also inhibited the phosphorylation of Iκ Bα kinase (IKK) and p65, and blocked the nuclear translocation of p65 protein. The findings indicate that GA inhibited the inflammatory response in LPS-stimulated microglial BV2 cells through the suppression of MAPK, Akt, and nuclear factor-κ B (NF-κ B) signaling pathways, suggesting that GA may serve as a potential therapeutic approach for the treatment of neuroinflammation-associated neurodegenerative diseases.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":"80 4","pages":"55-59"},"PeriodicalIF":1.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856003","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":"Effects of blood and brain midazolam concentrations on prolonged sedation in rats with low albumin levels.","authors":"T Yano, S Watanabe, G Kato, Y Toge, M Morita, H Mitome, N Hidaka, K Akira, M Tanaka","doi":"10.1691/ph.2025.4630","DOIUrl":"10.1691/ph.2025.4630","url":null,"abstract":"<p><p>Midazolam is a short-acting benzodiazepine widely used for sedation; however, its duration of action can be prolonged by various factors including hypoalbuminemia. Previous behavioral studies in rats with low albumin levels reported reduced muscle strength and spontaneous locomotion, but the relationship between hypoalbuminemia and midazolam pharmacokinetics remains unclear. This study investigated whether prolonged midazolam sedation in hypoalbuminemia correlates with unbound and brain midazolam concentrations. Low-albumin rats were generated using protein-controlled diets for 30 days. Midazolam (5 mg/kg, i. p.) was administered and total blood and brain concentrations were determined by high-performance liquid chromatography 10 and 60 minutes after administration. Compared to controls, low albumin rats showed significantly higher total blood concentrations at 60 minutes (0.27 ± 0.02 vs 0.12 ± 0.02 μg/mL) and brain concentrations (0.21 ± 0.02 vs 0.10 ± 0.03 μg/mL). Unbound concentrations remained below quantification limits due to ultrafiltration adsorption. Pharmacokinetic analysis revealed prolonged half-life and decreased clearance in low-albumin rats. These findings suggest that hypoalbuminemia prolonged midazolam actions through sustained blood and brain concentrations, likely due to increased initial unbound drug levels that rapidly distribute to the brain before accumulating in peripheral tissues. Clinicians should exercise caution when administering midazolam to patients with hypoalbuminemia.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":"80 4","pages":"51-54"},"PeriodicalIF":1.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855918","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":"<i>Cinchona</i> bark and quinine as psychiatric treatments in Portugal, 1700-1900.","authors":"M G Semedo, A L Pereira, J R Pita","doi":"10.1691/ph.2025.5015","DOIUrl":"10.1691/ph.2025.5015","url":null,"abstract":"<p><p><i>Cinchona</i> bark and its main medicinal derivative - quinine - are known antimalarials. Until the 20^th century, medicines with <i>Cinchona</i> bark or quinine were the only effective treatment for malaria used on a large-scale. However, <i>Cinchona</i> bark and quinine were also used in other diseases. Regarding psychiatric uses, in Britain, <i>Cinchona</i> bark was recommended in mania (17 th century) and nervous diseases (18 th century). Nevertheless, the full scope of <i>Cinchona</i> bark and quinine's proposed activity in psychiatric disorders has not been assessed. We aimed to investigate references to <i>Cinchona</i> bark and quinine's use and recommendation in psychiatric diseases and symptoms in Portugal, published in the 18^th and 19^th centuries. For this purpose, we reviewed Portuguese medical and pharmaceutical literature from this period. Our sources included books (namely pharmacopoeias) and periodical publications. We found 27 <i>Cinchona</i> bark or quinine medicines recommended in the treatment of psychiatric diseases and symptoms in Portugal. Those diseases included hysteria, hypochondria, and nervous diseases. <i>Cinchona</i> bark and quinine medicines were also advised in psychiatric symptoms such as anxiety-induced palpitations, melancholia, or hypochondriac or hysterical symptoms. For most of these medicines - 17 out of 27 - the authors mention their efficacy in clinical practice. Consequently, our research suggests that, in 18^th and 19^th -century Portugal, <i>Cinchona</i> bark and quinine medicines were a therapeutic option in various psychiatric conditions. Therefore, it is possible that <i>Cinchona</i> bark and quinine had additional therapeutic indications that remain unknown.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":"80 4","pages":"70-76"},"PeriodicalIF":1.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855916","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":"Therapeutic potential of basil (<i>Ocimum basilicum</i> L.) aqueous extract: Impact on glycemia and oxidative stress in normoglycemic and diabetic rats.","authors":"B Teofilović, A Tomas, N Martić, N Stilinović, I Čapo, N Grujić-Letić, E Gligorić, A Rašković","doi":"10.1691/ph.2025.4629","DOIUrl":"https://doi.org/10.1691/ph.2025.4629","url":null,"abstract":"<p><p>The prevention of nutrition-related diseases holds paramount significance for human well-being. Sweet basil (<i>Ocimum basilicum</i> L., Lamiaceae) emerges as a noteworthy candidate due to its robust antioxidant properties attributed to a high concentration of phenolic and flavonoid compounds, promising potential health benefits for humans. Notably, bile acids and their derivatives exert influence on the metabolic effects of both conventional and herbal drugs. The aim of this study was to examine the effects of administering an aqueous basil extract for seven days on glycemia and <i>in vivo</i> antioxidant activity in both healthy and diabetic animals, either alone or in combination with a bile acid derivative. The experimental design involved normoglycemic and diabetic Wistar rats subjected to a seven-day regimen of saline and basil water extract. Hyperglycemia was induced using alloxan. Following the treatment period, animals were euthanized by cardiopuncture, and serum analyses were conducted to assess fasting blood glucose levels and biochemical parameters. Additional assessments included oral glucose tolerance tests and antioxidative stress enzyme assays. The findings showed a significant hypoglycemic effect of the aqueous basil extract in both normoglycemic and diabetic animals. The extract also decreased lipid peroxidation and increased the activity of antioxidant enzymes. Basil extract treatment displayed protective effects on glycemia in both normoglycemic and diabetic animals, indicating considerable antioxidant potential. These effects were evident through increased antioxidant enzyme activity and decreased lipid peroxidation, affirming the beneficial impact of aqueous basil extract on health parameters.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":"80 1","pages":"17-23"},"PeriodicalIF":1.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037005","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":"Development and validation of a fast LC-MS/MS method for the quantitation of creatine and taurine in sports supplements.","authors":"R van der Merwe, W Liebenberg, H J R Lemmer, F van der Kooy","doi":"10.1691/ph.2025.4059","DOIUrl":"https://doi.org/10.1691/ph.2025.4059","url":null,"abstract":"<p><p>Sports supplements containing a combination of creatine and taurine have seen a dramatic rise in popularity. However, adequate analytical techniques for the quantification of these metabolites in tissue samples and supplements are essential. Liquid chromatography mass spectrometry offers a selective and sensitive alternative but to date, no method has been reported for the quantification of both compounds in combination. The main objective was to develop and validate a fast analytical method using LC-MS/MS and to test its suitability on seven commercial sports supplements. An isocratic method with a run time of 2.5 min using a hydrophilic interaction liquid chromatography column and multiple reaction monitoring transitions was developed and validated for linearity, precision, LOD and LOQ, ruggedness and recovery. Spiking experiments on seven commercial samples were conducted to test for possible ion enhancement/suppression. All validation parameters fell well within acceptable limits and the spiking recoveries of the commercial samples all fell between 81-116%. The seven products revealed large discrepancies between the measured values by as much as +99.66% for creatine and as low as -83.81% for taurine as compared to the label claims. These discrepancies highlight the importance of quality control, as inaccurate labelling could lead to unintentional overdosing, which may cause gastric issues and, in severe cases, kidney problems.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":"80 1","pages":"2-6"},"PeriodicalIF":1.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006847","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":"Coumarins attenuate intestinal motility by inhibiting TMEM16A.","authors":"Xiaojuan Zhu, Hao Wang, Bo Yu, Lingling Jin, Chao Qu, Hongyan Li, Hong Yang","doi":"10.1691/ph.2025.4544","DOIUrl":"https://doi.org/10.1691/ph.2025.4544","url":null,"abstract":"<p><p>Transmembrane 16A (TMEM16A) is highly expressed in interstitial cells of Cajal (ICC) and participates in ICC-mediated rhythmic contractile activity of intestinal smooth muscle. TMEM16A is also expressed in epithelium of intestine with a minor contributor to transepithelial fluid secretion, while other unidentified Ca²⁺ -activated Cl - channels (unCaCCs) are mainly responsible for this physiological process. TMEM16A/CaCCs dysfunction can lead to disorders of intestinal motility and transepithelial fluid secretion. TMEM16A/CaCCs regulators are important tools to identify unCaCCs and study the physiopathological functions related to TMEM16A/CaCCs. In the present study, coumarins were identified as TMEM16A inhibitors in a concentration- and time-dependent manner in TMEM16A-expressed Fischer rat thyroid (FRT) epithelial cells. Coumarins attenuated intestinal motility by inhibiting TMEM16A <i>in vivo</i> and <i>ex vivo</i>. Coumarins inhibited CaCCs-mediated Cl^- currents induced by ATP in T84 and HT-29 cells or by carbachol (CCh) in mouse colonic mucosa with reduction of ATP-induced increase of cytoplasmic Ca²⁺ concentration in HT-29 cells. Coumarins inhibited basolateral Ca²⁺ -activated K⁺ channels without affecting Na + /K + -ATPase activity in mouse colonic mucosa. Coumarins did not show inhibition of cystic fibrosis transmembrane conductance regulator (CFTR), but mild activation of CFTR-mediated Cl - currents under the low concentration forskolin (FSK) in CFTR-expressed FRT cells, while coumarins did not activate CFTR-mediated Cl- currents in mouse colonic mucosa. This study was the first to demonstrate that coumarins attenuate intestinal motility by inhibiting TMEM16A, which may provide a strategy for clinical drug intervention aimed at reducing secretory diarrhea.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":"80 1","pages":"10-16"},"PeriodicalIF":1.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988612","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":"Pharmacokinetic study of two sulfamethoxazole-phytochemical antimicrobial conjugates in mice.","authors":"J Yang, B Ling, S B Chidambaram, M K Sakharkar","doi":"10.1691/ph.2025.5510","DOIUrl":"https://doi.org/10.1691/ph.2025.5510","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) has emerged to be a big threat to both human and animal health. Along the tighter control on antibiotic use, developing novel therapeutic agents and approaches is crucial for combating AMR. We recently designed and synthesized several antibiotic-phytochemical conjugates which exhibited potent antimicrobial activities. To understand their pharmacological behavior and obtain a guideline for further drug development, we undertook a pharmacokinetic study on sulfamethoxazole-gallate and sulfamethoxazole-caffeate. C_max was determined to be 842 ± 544 ng/mL at dose of 1500 mg/kg and 733 ± 477 ng/mL at dose of 2000 mg/kg for sulfamethoxazole-gallate and 211 ± 100 at a dose of 150 mg/kg and 755 ± 705 ng/mL at dose of 300 mg/kg for sulfamethoxazole-caffeate. T_max was 1 h for sulfamethoxazole-gallate under both doses and 0.5 h for sulfamethoxazole-caffeate under both doses. Since C_max was significantly lower than the <i>in vitro</i> MIC for both conjugates, more formulations and administration routes such as IV injection will be investigated in our future studies.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":"80 1","pages":"7-9"},"PeriodicalIF":1.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012474","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":"Disproportionality analysis of cardiac adverse events associated with sorafenib using Spontaneous Reporting Database in Japanese.","authors":"Y Kanbayashi, R Kano, E Tsuchiya, H Wakabayashi, Y Kawahara, T Shimizu, M Uchida","doi":"10.1691/ph.2025.4624","DOIUrl":"https://doi.org/10.1691/ph.2025.4624","url":null,"abstract":"<p><p>This study was conducted to examine the disproportionality, times to onset, incidence rates, and outcomes of sorafenib-associated cardiac AEs, using the Japanese Adverse Drug Event Report database. We analyzed data for the period between April 2004 and May 2023. Data on cardiac AEs were extracted and the relative disproportionality of AEs was estimated using reporting odds ratios (RORs). We analyzed 2,230,863 reports and identified 8,374 reports of AEs associated with sorafenib, including 318 cardiac AEs. Signals were detected for seven cardiac AEs: hypertension, cardiac failure congestive, myocardial infarction, acute myocardial infarction, angina pectoris, myocardial ischaemia, and angina unstable. Among these, fatal outcomes were observed for cardiac failure congestive, myocardial infarction, acute myocardial infarction, and myocardial ischaemia. Histograms of median times to onset for the seven detected cardiac AE signals showed that AEs occurred at a median of 9-159 days after sorafenib administration. Weibull distributions showed that the incidence of all these AEs occurred constantly throughout the exposure period (random failure type). In conclusion, we focused on cardiac AEs associated with sorafenib as post-marketing AEs. Some cases could experience serious outcomes after sorafenib administration. Patients should be monitored for signs of onset for these AEs not only at the start of administration, but also over an extended period.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":"80 1","pages":"29-32"},"PeriodicalIF":1.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006848","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}