International journal of clinical pharmacology and therapeutics最新文献

{"title":"Degree of serum LDL cholesterol reduction by simvastatin and ezetimibe is dependent on baseline LDL cholesterol concentration but not on baseline values and changes in cholesterol synthesis and absorption parameters.","authors":"Dieter Lütjohann, Frans Stellaard","doi":"10.5414/CP204536","DOIUrl":"10.5414/CP204536","url":null,"abstract":"<p><strong>Objective: </strong>We questioned whether the baseline status of low-density lipoprotein cholesterol (LDL-C), cholesterol synthesis and absorption, and the changes in these parameters determine the change in serum LDL-C under statin or ezetimibe treatment or under combination treatment.</p><p><strong>Materials and methods: </strong>37 mildly hypercholesterolemic healthy male subjects were studied under placebo, simvastatin (20 mg/d), ezetimibe (10 mg/d), and combination treatment. We correlated the change of LDL-C (ΔLDL-C) under treatment with the placebo end values of LDL-C (baseline), whole-body cholesterol synthesis, and hepatic cholesterol synthesis (serum lathosterol to cholesterol ratio) as well as fractional absorption rate (FAR) of cholesterol and serum campesterol to cholesterol ratio. The change in serum LDL-C was also correlated with the changes in synthesis and absorption parameters.</p><p><strong>Results: </strong>ΔLDL-C was highly negatively related to baseline LDL-C under ezetimibe (p < 0.0001), simvastatin (p < 0.0001), and combination treatment (p < 0.0001). Under combination treatment, LDL-C lowering appears possible from baseline values of 10 mg/dL upwards, while ΔLDL-C was independent of the baseline value (-50 to -60%). ΔLDL-C was positively associated with placebo FAR under ezetimibe (p = 0.0106) and combination treatment (p = 0.0457). No associations were found between ΔLDL-C and baseline values for synthesis nor between ΔLDL-C and changes in synthesis and absorption surrogate markers.</p><p><strong>Conclusion: </strong>Under ezetimibe, simvastatin, and combination treatment, ΔLDL-C is predominantly dependent on the baseline LDL-C concentration. We hypothesize that the concentration gradient between serum LDL-C and hepatic cellular cholesterol determines the efficiency of serum LDL-C lowering. Combination treatment is the preferred treatment.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"295-306"},"PeriodicalIF":0.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865515","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":"Activated charcoal helps in the diagnosis of dabigatran overdose: A case study.","authors":"Ning Zhang, Weihua Niu, Haiqing Zhang, Songsong Lu","doi":"10.5414/CP204493","DOIUrl":"10.5414/CP204493","url":null,"abstract":"<p><p>The direct-acting oral anticoagulant dabigatran etexilate (DE) targets thrombin and is used widely to prevent thromboembolism. A 79-year-old man was admitted to the Emergency Department due to anuria for 2 days. An urgent laboratory examination revealed a serum creatinine concentration of 888 µmol/L. He was diagnosed with acute exacerbation of chronic renal insufficiency. During continuous renal replacement therapy (CRRT), the coagulation test showed a severe reduction in the fibrinogen level as well as a significantly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT). The patient had been taking DE (110 mg twice daily) for a long time and had not suspended the medication or reduced the dose during the worsening of anuria. Therefore, it should be evaluated before considering plasma replacement therapy for the patient, whether the abnormal coagulation parameters were induced by interference of excessive DE. Tentatively, we used activated charcoal to treat the plasma and then retested the fibrinogen, PT, and APTT. Results showed that the coagulation indices nearly returned to normal. The present case indicated that activated charcoal could adsorb DE in plasma effectively and eliminate its interference with coagulation test results, thereby providing support for clinical diagnosis and treatment.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"334-338"},"PeriodicalIF":0.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897411","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":"Primary and secondary prevention of stroke and cardiovascular events using evolocumab and alirocumab: Meta-analysis of randomized controlled trials.","authors":"Kwang-Hee Shin, Hye Duck Choi","doi":"10.5414/CP204506","DOIUrl":"10.5414/CP204506","url":null,"abstract":"<p><strong>Objectives: </strong>Although the clinical role of protein convertase subtilisin kexin type 9 (PCSK9) inhibitors for cholesterol management is increasing, the post-marketing period of use is short compared to other lipid-lowering drugs, so there is still insufficient evidence for their efficacy and safety. In this meta-analysis, we evaluated preventive effects of stroke and cardiovascular (CV) events using evolocumab and alirocumab.</p><p><strong>Materials and methods: </strong>We assessed the relative risk of stroke and CV events after alirocumab or evolocumab treatment in individuals with or without clinical CV diseases compared with that in controls. In addition, we evaluated the relative risk of hemorrhagic stroke.</p><p><strong>Results: </strong>A total of 25 articles were included (median of study duration = 52 weeks). The risk of stroke was significantly decreased after treatment with alirocumab or evolocumab (primary prevention in patients without CV diseases: RR = 0.733; 95% CI, 0.618 - 0.870; secondary prevention in patients with CV diseases: RR = 0.703; 95% CI, 0.562 - 0.880). The risk of CV events also significantly decreased in patients treated with alirocumab or evolocumab (primary prevention: RR = 0.818; 95% CI, 0.777 - 0.861; secondary prevention: RR = 0.725; 95% CI, 0.578 - 0.910). The relative risk of hemorrhagic stroke was not significantly different between PCSK9 inhibitor-treated patients and controls (RR = 1.041; 95% CI, 0.690 - 1.573).</p><p><strong>Conclusion: </strong>Our findings indicate that evolocumab and alirocumab are significantly effective without increasing the risk of hemorrhagic stroke. Based on this, the PCSK9 inhibitors can be highly recommended for cholesterol management.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"250-258"},"PeriodicalIF":0.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140287456","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":"Balancing efficacy and adverse reactions using everolimus in a patient with metastatic malignant insulinoma: Case report.","authors":"Siham Rouf, Khadija Boujtat, Tijani El Harroudi, Hanane Latrech","doi":"10.5414/CP204503","DOIUrl":"10.5414/CP204503","url":null,"abstract":"<p><strong>Introduction: </strong>Malignant insulinoma is a rare neuroendocrine tumor responsible for excessive insulin secretion and life-threatening hypoglycemia episodes. Computed tomography (CT) of the abdomen can identify a pancreatic tumor corresponding to insulinoma. Loco-regional metastases define the metastatic cases. The first-line therapeutic approach is surgery, while other medical treatments like diazoxide and everolimus play also a role. These treatments have shown efficacy in regulating blood glucose and, to some extent, controlling tumor progression.</p><p><strong>Case presentation: </strong>We present the case of a 48-year-old female who was admitted for severe hypoglycemia episodes. She presented neuroglycopenic symptoms without any other clinical features. High levels of C-peptide and insulin during severe hypoglycemia confirmed the presence of endogenous hyperinsulinism. The CT scan of the abdomen confirmed the existence of an insulinoma along with several hepatic metastases. Surgery was proposed as a first-line approach. However, due to the persistent occurrence of severe hypoglycemia episodes, other treatment options were necessary such as diazoxide and everolimus. Diazoxide caused a significant improvement in the patient's blood glucose levels. Nonetheless, glycemic control was unsustainable, obligating the switch to everolimus, which showed better control of blood glucose levels with challenging management due to the appearance of grade 3 stomatitis as a side effect. The patient died 1 year after the diagnosis due to tumor progression.</p><p><strong>Conclusion: </strong>Balancing the benefits of enhanced glycemic control with the difficulties posed by side effect management of everolimus underscores the need to carefully consider both efficacy and potential adverse events.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"278-283"},"PeriodicalIF":0.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021679","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":"Efficacy and safety of antiplatelet therapy in COVID-19: Insights from a meta-analysis of randomized controlled trials.","authors":"Guoying Kao, Yunlin Chen, Jinqi Fan","doi":"10.5414/CP204497","DOIUrl":"10.5414/CP204497","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 induces a pro-coagulant state with thrombotic events. This meta-analysis explores the efficacy and safety of antiplatelet-based therapy in COVID-19 patients through randomized controlled trials (RCTs).</p><p><strong>Materials and methods: </strong>A systematic literature search until March 10, 2023, identified 7 RCTs involving 23,415 inpatients. Of these, 11,891 received antiplatelet-based treatment, and 11,524 received placebo/other drugs. Statistical analysis was performed using Review Manager 5.4.</p><p><strong>Results: </strong>The included trials involved patients with a mean age ranging from 54.3 to 62.0 years and a prevalence of hypertension ranging from 10.9 to 65.0% and coronary artery disease ranging from 3.2 to 32.7%. The pooled analysis showed no significant difference in overall mortality between groups (RR 1.0, 95% CI 0.99 - 1.01, p = 0.76). However, antiplatelet therapy significantly reduced major thrombotic events (RR 0.86, 95% CI 0.75 - 0.99, p = 0.04). Conversely, it increased major bleeding risks (RR 1.62, 95% CI 1.24 - 2.12, p = 0.0005). There was no significant difference in the incidence of invasive mechanical ventilation and respiratory death.</p><p><strong>Conclusion: </strong>Antiplatelet therapy does not confer mortality benefit in COVID-19 patients but lowers major thrombotic events while increasing major bleeding risks. Ongoing large RCTs will provide more information on the therapeutic value of this therapy.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"195-203"},"PeriodicalIF":0.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101475","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":"Low albumin combined with low-molecular-weight heparin as risk factors for liver injury using azvudine: Evidence from an analysis of COVID-19 patients in a national prospective pharmacovigilance database.","authors":"Hong Lu, Ying Zeng, Qun-Zhi Shi, Lin Liu, Yong-Qing Gong, Sen Li, Pan Yan","doi":"10.5414/CP204544","DOIUrl":"10.5414/CP204544","url":null,"abstract":"<p><strong>Objective: </strong>Azvudine is an effective treatment for patients infected with common COVID-19. However, physicians have reported a series of adverse reactions, including multiple cases of liver injury, caused by azvudine in clinical practice. This study assessed the incidence, clinical features, and associated risk factors of liver injury induced by azvudine in real-world settings, offering guidance for safe clinical use.</p><p><strong>Materials and methods: </strong>This study utilized the Chinese Hospital Pharmacovigilance System (CHPS) to retrospectively analyze the treatment of COVID-19 patients with azvudine at Changsha Central Hospital from December 19, 2022, to June 6, 2023. A case-control study was conducted to analyze the occurrence of azvudine-induced liver injury in COVID-19 patients who triggered a CHPS alert compared to normal COVID-19 patients.</p><p><strong>Results: </strong>Among the total of 2,141 COVID-19 patients, 31 (1.45%) developed azvudine-induced liver injury, which is classified as an occasional adverse reaction. Liver injury was observed in 93.55% of patients between days 4 and 12 of the azvudine treatment, with elevated transaminases as the primary clinical manifestation. Univariate and binary logistic regression analyses indicated that low albumin levels and co-administration of low-molecular-weight heparin were statistically significant risk factors (p < 0.05).</p><p><strong>Conclusion: </strong>This study represents the first investigation of azvudine-induced liver injury and high-risk patients using the CHPS. The findings provide valuable insights to promote the safety of anti-COVID-19 drugs, serving as an important reference for future drug safety measures.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"222-228"},"PeriodicalIF":0.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021682","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":"Comparison of vancomycin area under the curve calculated based on Bayesian approach versus equation-based approach.","authors":"Eojin Lee, Uijeong Yu, Ji In Park, Sang-In Park","doi":"10.5414/CP204508","DOIUrl":"10.5414/CP204508","url":null,"abstract":"<p><strong>Objective: </strong>Area under the curve (AUC)-based vancomycin dose adjustment is recommended to treat methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) infections. AUC estimation methods include Bayesian software programs and simple analytical equations. This study compared the AUC obtained using the Bayesian approach with that obtained using an equation-based approach.</p><p><strong>Materials and methods: </strong>Patients receiving intravenous vancomycin for MRSA infection were included. Peak and trough levels were measured for each patient on days 3, 7, and 10 post vancomycin dosing (day 1). AUC was calculated using software based on the Bayesian method (MwPharm Online) and an equation-based calculator, Stanford Health Care (SHC) calculator.</p><p><strong>Results: </strong>The AUC estimated using MwPharm Online was similar to that estimated using the SHC calculator. The geometric mean ratio (GMR) and their 90% confidence intervals (90% CI) were 1.08 (1.05 - 1.11), 1.03 (0.99 - 1.07), and 0.99 (0.94 - 1.05) at days 3, 7, and 10, respectively. Furthermore, according to the software used, there were no significant differences in the proportions of patients in the categories \"within\" and \"below or above\" the AUC target range. Additionally, trough levels predicted by both software programs were lower than the observed ones. Still, there was no significant difference between the predicted and observed peak levels for both software programs on day 10.</p><p><strong>Conclusion: </strong>AUC calculated using the Bayesian software allows for calculation with samples at a non-steady state, can integrate covariates, and is interconvertible with that estimated using an equation-based calculator, which is simpler and relies on fewer assumptions. Therefore, either method can be used, considering each method's strengths and limitations.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"204-212"},"PeriodicalIF":0.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706702","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":"Evaluation of the risk factors for the failure of a single prophylactic dose of anticholinergic drugs for irinotecan-induced cholinergic symptoms.","authors":"Takuya Watanabe, Yoshitaka Saito, Yoh Takekuma, Yasushi Shimizu, Ichiro Kinoshita, Yoshito Komatsu, Mitsuru Sugawara","doi":"10.5414/CP204531","DOIUrl":"10.5414/CP204531","url":null,"abstract":"<p><strong>Objective: </strong>Irinotecan (IRI) is an anticancer drug that is frequently used to treat colorectal, gastric, and pancreatic cancers. Its side effects include cholinergic symptoms, such as diarrhea, abdominal pain, nausea, and hyperhidrosis. Anticholinergic medicines are frequently used for treatment or prophylaxis; however, the risk factors for the failure of a single prophylactic anticholinergic administration remain unclear. Moreover, an appropriate anticholinergic drug for prophylaxis remains unknown. Thus, we aimed to identify the risk factors associated with the failure of a single prophylactic dose of anticholinergic drugs for IRI-induced cholinergic symptoms and to evaluate the usefulness of multiple prophylactic doses of anticholinergic drugs.</p><p><strong>Materials and methods: </strong>Patients who underwent IRI treatment for colorectal, gastric, or pancreatic cancer and received prophylactic anticholinergic drugs for IRI-induced cholinergic symptoms (n = 135) were retrospectively evaluated. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for failure of a single prophylactic dose of anticholinergic drugs. We also evaluated the efficacy of multiple prophylactic anticholinergic drug administration.</p><p><strong>Results: </strong>Based on univariate and multivariate analyses, colorectal cancer, female sex, and prophylactic use of scopolamine butyl bromide were identified as risk factors for failure of a single prophylactic dose of anticholinergic drugs. The efficacy of multiple prophylactic doses was confirmed to be 95% of the patients who had a single prophylactic failure due to temporary effect but symptom appearance after a certain period of time (wearing-off).</p><p><strong>Conclusion: </strong>We determined that colorectal cancer, female sex, and prophylactic use of scopolamine butyl bromide were risk factors associated with the failure of a single prophylactic dose of anticholinergic drugs, and that multiple prophylactic doses for wearing-off can be a promising method.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"213-221"},"PeriodicalIF":0.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021681","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":"Clinical implications and future prospects of levonorgestrel and piroxicam as a combined emergency contraceptive regimen.","authors":"Jiawei Ke, Jingrui Cai, Xiaolin Liu, Liwen Chen, Tianhui Liu, Zhipeng Ruan, Chengfei Zhao","doi":"10.5414/CP204537","DOIUrl":"10.5414/CP204537","url":null,"abstract":"","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"229-230"},"PeriodicalIF":0.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706701","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":"Comparison of SB17 and reference ustekinumab in healthy adults: A randomized, double-blind, single-dose, phase I study.","authors":"Hansol Jeong, Taeseung Kang, Jiyoon Lee, Seongsik Im","doi":"10.5414/CP204492","DOIUrl":"10.5414/CP204492","url":null,"abstract":"<p><strong>Objective: </strong>This study compared the pharmacokinetic (PK) characteristics of SB17 (Samsung Bioepis, Incheon, Republic of Korea), a proposed biosimilar of ustekinumab (UST) against reference UST (Stelara, Janssen Biotech, Horsham, PA, USA).</p><p><strong>Materials and methods: </strong>This double-blind, three-arm, parallel-group, single-dose study randomized 201 healthy adult subjects 1 : 1 : 1 to receive 45 mg of SB17, European Union-sourced UST (EU-UST) or United States of America-sourced UST (US-UST) via subcutaneous (SC) injection. Primary endpoints were area under the concentration-time curve from time zero to infinity (AUC_inf) and maximum serum concentration (C_max). Safety, tolerability, and immunogenicity were investigated.</p><p><strong>Results: </strong>All 90% confidence intervals (CIs) for the ratios of AUC_inf and C_max between groups were within the predefined bioequivalence margin of 0.8 - 1.25. The geometric LSMeans ratios of AUC_inf and C_max were 0.99 and 0.90 for SB17/EU-UST, 1.01 and 0.94 for SB17/US-UST, and 1.02 and 1.05 for EU-UST/US-UST, respectively. The proportion of subjects with treatment-emergent adverse events (TEAEs) was comparable between SB17, EU-UST, and US-UST (68.7, 58.2, and 65.7%). No deaths, serious adverse events (SAEs), or severe TEAEs were reported. The incidence of subjects testing positive for post-dose anti-drug antibodies (ADAs) was 26.9%, 34.3%, and 34.3% in the SB17, EU-UST, and US-UST groups, respectively. Among the subjects with a positive ADA result at day 99/end of study, 53.8% (SB17 n = 5, EU-UST n = 12, and US-UST n = 11) were positive for neutralizing antibodies (NAbs).</p><p><strong>Conclusion: </strong>This study demonstrated bioequivalence of SB17, EU-UST, and US-UST in terms of PK. Safety, tolerability, and immunogenicity were also comparable between all groups.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"231-240"},"PeriodicalIF":0.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11036876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086818","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}