International journal of clinical pharmacology and therapeutics最新文献

{"title":"Bioequivalence study of two formulations of afatinib dimaleate tablets in healthy subjects under fasting conditions: A randomized, open-label, single-dose, crossover trial.","authors":"Yanping Liu, Lang Lü, Man Xu, Juanmin Tao, Yuping Ning, Yan Shi, Yanfen Dong, Qingqing Cao, Jun Ma, Yan Qiu","doi":"10.5414/CP204514","DOIUrl":"10.5414/CP204514","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the bioequivalence of two different afatinib dimaleate formulations in healthy Chinese subjects under fasting conditions and to assess their pharmacokinetic and safety profiles.</p><p><strong>Materials and methods: </strong>This randomized, open-label, 2-period, crossover, bioequivalence study included 32 healthy Chinese subjects. The subjects were assigned to receive a single 40-mg dose of generic or brand-named afatinib dimaleate tablet. Blood samples were collected pre-dose and up to 120 hours after dosing. Healthy subjects orally took the trial preparation (T) (afatinib maleate tablets developed by Jiangxi Shanxiang Pharmaceutical Co., Ltd., Gan Zhou, China) and the reference preparation (R) (afatinib maleate tablets developed by Boehringer Ingelheim Pharma GmbH & Co., Ingelheim, Germany) under fasting conditions in the appropriate period according to the randomization. We measured the blood concentrations, calculated the pharmacokinetic parameters of the two preparations in the human body, and evaluated whether formulations were bioequivalent. Safety of the preparations in healthy subjects was monitored during the whole trial. Safety assessment was conducted by vital signs, physical examination, laboratory examination, and 12-lead electrocardiogram during the study, i.e., from the time the subject received the test drug to the end of the last visit.</p><p><strong>Results: </strong>Under fasting conditions, the 90% confidence intervals (CIs) of the geometric mean ratios of the test/reference for afatinib dimaleate were 93.34 - 103.92% for AUC_0-t, 90.26 - 105.52% for C_max, and 93.49 - 104.05% for AUC_0-∞.</p><p><strong>Conclusion: </strong>The 90% CI for the geometric mean ratios (test/reference) of C_max, AUC_0-t, and AUC_0-∞ were within the range of 80.00 - 125.00%, indicating that the test formulation was equivalent to the reference formulation in healthy Chinese subjects under fasting conditions. Both products were similar in terms of safety.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"479-485"},"PeriodicalIF":0.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999825","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":"Pulmonary fibrosis insights and therapy targets from disease models and administration of the lipophilic diterpene, sodium tanshinone IIA sulfonate: Review and meta-analysis.","authors":"Li-Ying Peng, Jun-Jun Shi, Yue Liang, Yang Li, Yan Tang, Tuo Kai, Andong Yang, Zi-Yue Xiong","doi":"10.5414/CP204622","DOIUrl":"10.5414/CP204622","url":null,"abstract":"<p><p>Pulmonary fibrosis (PF) is a chronic and progressive pulmonary interstitial disease of unknown etiology and is also a sequela in severe patients with the Coronavirus Disease 2019 (COVID-19). Seven databases were systematically searched to evaluate the preclinical evidence of Tanshinone IIA (Tan IIA) on PF. The quality of the included studies was assessed using a 10-item risk of bias tool, and data were analyzed using RevMan 5.3 software. 22 experiments from 12 studies on a total of 248 animals were included. The results showed that PF phenotype, such as fibrotic score, collagen I (Col-I), collagen III (Col-III), hydroxyproline (Hyp), in the group treated with Tan IIA were significantly lower than those in the model group (p < 0.00001). The potential mechanisms of Tan IIA improvement of PF involve reducing inflammation, antioxidation, and suppressing activation of transforming growth factor beta 1 (TGF-β1). The subgroup analysis of different models, different rat species, and different dosage time showed significant reduction in fibrotic scores and Hyp levels with Tan IIA. The preclinical evidence indicated that Tan IIA might be a potent and promising agent for PF, but this conclusion should be further confirmed with more research.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"460-478"},"PeriodicalIF":0.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906610","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":"Rational use of short-term anorectic drugs for one-year effective treatment of obesity: An analysis of four studies.","authors":"Cynthia Galicia-Quintanar, Héctor Isaac Rocha-González, María Elena Sánchez Mendoza, Jesús Arrieta-Valencia, Juan Rodríguez-Silverio, Geovanna Nallely Quiñonez-Bastidas, Juan Carlos Huerta-Cruz, Lina Marcela Barranco-Garduño, Juan Gerardo Reyes-García","doi":"10.5414/CP204585","DOIUrl":"10.5414/CP204585","url":null,"abstract":"<p><strong>Background: </strong>Obesity is a complex disease for which pharmacotherapy is often used. Anti-obesity drugs (AODs) are characterized by inducing a variable inter-subject body weight reduction (BWR), the attainment of a plateau after their maximal effect is achieved, and weight regain after drug discontinuation, which complicate individualized treatment of obesity.</p><p><strong>Objective: </strong>This exploratory analysis aimed to compare the first-month body weight reduction in kg (1mo-BWRkg) and tolerance development (moT) of four known interventions with low (placebo), intermediate (phentermine or mazindol monotherapy), and high (5 active ingredients fixed-dose combination) efficacy, as predictors of their 6-month body weight reduction efficacy in percent (6mo-BWR%). In addition, a detailed analysis of the 6-to-12-month BWR follow-up in subjects under orlistat or diet and exercise regimens was performed.</p><p><strong>Materials and methods: </strong>The analysis included 662 adult subjects with obesity. After the construction of average efficacy and weight rebound curves, subjects were grouped into various 1mo-BWRkg, moT, and 6mo-BWR% intervals, or 6-month body weight rebound parameters for further evaluation.</p><p><strong>Results: </strong>The 6mo-BWR% efficacy level of interventions was confirmed, although a general high intersubject variation was observed. 1mo-BWRkg + moT was found as an acceptable predictor of 6mo-BWR%. Between 50 and 80% of the 6-to-12-month follow-up completers maintained at least 5% BWR%.</p><p><strong>Conclusion: </strong>Short-term AODs are useful adjuvants for the 1-year rational treatment of obesity. 1mo-BWRkg + moT is an acceptable parameter to predict the 6mo-BWR% efficacy of these interventions.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"435-447"},"PeriodicalIF":0.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751653","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":"Adequate IVIG dosing is associated with an improved long-term outcome in secondary immunodeficiency: A prospective, non-interventional study.","authors":"Artur Bauhofer, Ümniye Balaban, Sonja Schimo, Monika Mayer, Jörg Schüttrumpf, Stephan Borte","doi":"10.5414/CP204595","DOIUrl":"10.5414/CP204595","url":null,"abstract":"<p><strong>Objective: </strong>To assess the safety, tolerability, and effectiveness of the intravenous immunoglobulin (IVIG) Intratect 50 g/L in immunoglobulin replacement therapy (IgRT) in a prospective, large-scale non-interventional study (NIS). The analysis focused upon patients with secondary immunodeficiency (SID), the most frequent indication for IgRT in this NIS.</p><p><strong>Materials and methods: </strong>Patients were enrolled at 123 centers in Germany. Each patient received IVIG as prescribed by the physician, guided by the Summary of Product Characteristics. Data were acquired from medical records and patients' questionnaires.</p><p><strong>Results: </strong>In the NIS, 3,563 patients were documented. The main indication for IgRT was SID (73.2%), followed by primary immunodeficiency (14.7%), immune thrombocytopenia (5.8%), and other indications (6.2%). Among the SID patients, 52.9% were male, mean age was 66.5 years, and most (63.8%) were IVIG-naïve. Their annual infection rate improved from 3.7 before documentation in the NIS to 1.1 during the first year of the study. IgG trough plasma levels increased during treatment (> 6 g/L: 44.5% of SID patients at study entry and 64.8% in long-term treatment) and were associated with a trend toward reduced infection rate (p = 0.08). A 1-year infection analysis showed a significantly lower infection risk in the medium- and high-dose groups than in the low-dose group (p = 0.028 and p = 0.017, respectively). Patients' treatment satisfaction and quality of life improved from baseline. Adverse drug reactions (ADRs) in SID occurred at a low frequency with 0.8% at infusion level. On the patient level, ADRs occurred in 251 (15.3%) SID patients, with chills (7.4%) and pyrexia (0.9%) reported most frequently.</p><p><strong>Conclusion: </strong>Effectiveness, safety, and quality of life confirmed the positive benefit-risk profile of IgRT. Higher IVIG dosages per body weight led to higher IgG plasma trough levels, in turn leading to reduced infection rates. Obese patients may need body-weight-adjusted treatment to reduce the risk of infection.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"448-459"},"PeriodicalIF":0.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792465","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":"Pharmacokinetic, bioequivalence, and safety assessments of two brands of 30-mg nifedipine controlled-release formulations in Chinese healthy subjects.","authors":"Huan Lu, Fei Zhou, Cuijie Rui, Hen You, Wenhao Zhang, Yaxin Zhang, Juefang Ding, Shunbo Zhao, Qiang Wu","doi":"10.5414/CP204605","DOIUrl":"10.5414/CP204605","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to analyze the pharmacokinetic (PK) characteristics, safety, and bioequivalence (BE) of a test (T) preparation of a nifedipine controlled-release tablet and the reference (R) drug (Adalat GTIS) in Chinese study participants in the context of fasting and postprandial states.</p><p><strong>Materials and methods: </strong>An open-label, single-center, randomized, single-dose, two-period study was designed including two separate arms, one with administration under fasting conditions and one with administration under postprandial conditions (high-fat, high-calorie breakfast). After oral administration, the nifedipine concentrations in plasma were quantitatively analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) at regular intervals. Primary PK parameters, including the area under the concentration curve from 0 to infinity (AUC_0-∞), the area under the concentration profile from 0 to the last measurable concentration time (AUC_0-t), and maximal measured plasma concentration (C_max) were log-transformed with BE limits of 80 - 125% to evaluate BE. All adverse events (AEs) were wholly supervised.</p><p><strong>Results: </strong>The PK profiles of the T and R formulations were comparable to each other under both fasting and postprandial conditions. The 90% confidence intervals (CIs) of the AUC_0-∞, AUC_0-t, and C_max were 92.69 - 106.06%, 93.32 - 107.05%, and 99.53 - 116.71%, respectively, under the fasting state. The 90% CIs of the AUC_0-∞, AUC_0-t, and C_max were 105.05 - 117.40%, 105.43 - 117.82%, and 102.66 - 116.30%, respectively, in the postprandial arm. 47 cases of drug-associated AEs were noted in the entire research.</p><p><strong>Conclusion: </strong>Under both the fasting and postprandial states, the two nifedipine controlled-release formulations were bioequivalent and safe in healthy Chinese subjects.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"486-496"},"PeriodicalIF":0.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792466","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 case study of impaired consciousness caused by alcohol consumption in a pediatric patient taking high-dose cefixime.","authors":"Li Zheng, Gen Li, Liaoyun Zhang","doi":"10.5414/CP204623","DOIUrl":"10.5414/CP204623","url":null,"abstract":"<p><p>A variety of drugs have been known to induce disulfiram-like reactions in individuals exposed to ethanol, including certain cephalosporin antibiotics with methylthiotetrazole (MTT) substituents or methylthiodioxotriazine (MTDT) rings. Among cephalosporins, cefixime is known to cause fewer disulfiram-like reactions. This case report, the first involving a pediatric patient, presents the scenario of a 14-year-old female who exhibited drowsiness, loss of consciousness, and cold extremities within an hour after ingesting 9 cefixime capsules. Upon admission, drug intoxication was considered, prompting immediate gastric lavage and toxicology tests, which revealed the presence of both cefixime and alcohol. Subsequent monitoring of vital signs, rehydration, and symptomatic treatments aimed at facilitating toxic excretion were administered during hospitalization. Following initial assessment by a clinical pharmacist, drug intoxication was deemed improbable, though an atypical disulfiram-like reaction or alcohol intoxication could not be ruled out. Further evaluation, coupled with the child's cefixime overdose, suggested an atypical disulfiram-like reaction. This case underscores the potential for disulfiram reactions even with cephalosporins lacking MTT substituents or MTDT rings. Notably, it is the first report of an atypical disulfiram-like reaction triggered by alcohol consumption following cefixime overdose, emphasizing the importance of caution in cefixime usage and avoidance of alcohol or alcohol-containing substances.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"427-430"},"PeriodicalIF":0.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734070","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":"Evidence-based clinical pharmacology using network analysis of the curcuma-containing traditional Chinese medication Changpu-Yujin: Efficacy in the treatment of insomnia.","authors":"Jianran Ma, Qian Hu, Qing Hu, Zhijie Li","doi":"10.5414/CP204535","DOIUrl":"10.5414/CP204535","url":null,"abstract":"","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"431-434"},"PeriodicalIF":0.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497996","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":"Population pharmacokinetic study and application of ticagrelor and AR-C124910XX after percutaneous coronary intervention in Chinese patients with acute coronary syndrome.","authors":"Meng Liu, Jun Qin, XiaoQian Chu, NaiDong Chen, Qiong Jie, ShaoJun Zheng","doi":"10.5414/CP204550","DOIUrl":"10.5414/CP204550","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to understand the pharmacokinetics of ticagrelor in Chinese patients with acute coronary syndrome (ACS), identify influencing factors, and inform ticagrelor treatment optimization.</p><p><strong>Materials and methods: </strong>Data from 195 ACS patients, including 491 plasma ticagrelor concentration timepoints and clinical information, were analyzed using NONMEN for pharmacokinetic (PK) parameter factors. The model underwent internal validation with bootstrap methodology.</p><p><strong>Results: </strong>The PK curve of ticagrelor was well delineated using a one disposition compartment model with first-order absorption rate constant, 0.67/h. When the direct bilirubin levels and white plasma cell counts increased, female patients showed decreased glomerular filtration rate, decreased ticagrelor clearance rate, and increased exposure. When the direct bilirubin levels increased and body weight and hemoglobin decreased, rs6787801 was GG compared with AA and GA, the ticagrelor metabolite clearance rate decreased and exposure increased.</p><p><strong>Conclusion: </strong>The study offers key insights into ticagrelor's dose-exposure relationship post-percutaneous coronary intervention in ACS patients, highlighting factors critical for personalized treatment strategies.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"412-422"},"PeriodicalIF":0.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734071","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 decision tree model for predicting high mono-N-desethylamiodarone concentrations and reducing tissue toxicity in patients with low-dose amiodarone therapy: A multicentral retrospective cohort study.","authors":"Yuki Asai, Hiroki Arihara, Saki Omote, Ena Tanio, Saena Yamashita, Takashi Higuchi, Ei Hashimoto, Momoko Yamada, Hinako Tsuji, Yoshihiro Kondo, Makoto Hayashi, Takumi Tashiro, Yuji Hayakawa, Yoshiaki Yamamoto, Takuya Iwamoto","doi":"10.5414/CP204571","DOIUrl":"10.5414/CP204571","url":null,"abstract":"<p><strong>Objective: </strong>High plasma levels of mono-<i>N</i>-desethylamiodarone (MDEA), an active amiodarone metabolite, may be associated with tissue toxicity in heart failure (patients with heart rhythm disturbances); therefore, a tool that can identify patients for whom therapeutic drug monitoring (TDM) of MDEA is required. This multicenter study aimed to develop a decision tree (DT) model that can identify patients with heart rhythm disturbances at high MDEA concentrations.</p><p><strong>Materials and methods: </strong>A multicenter retrospective cohort study was conducted, including 157 adult patients with heart failure who received oral amiodarone treatment. A χ² automatic interaction-detection algorithm was used to construct a DT model. In the DT analysis, the dependent variable was set as an MDEA trough plasma concentration of ≥ 0.6 μg/mL during the steady-state period. Explanatory variables were selected as factors with p < 0.05 in multivariate logistic regression analysis.</p><p><strong>Results: </strong>The adjusted odds ratios for the daily dose of amiodarone and body mass index were 1.01 (95% coefficient interval: 1.008 - 1.021, p < 0.001) and 0.91 (95% confidence interval: 0.834 - 0.988, p = 0.025), respectively. For DT analysis, the risk of reaching plasma MDEA concentrations ≥ 0.6 μg/mL was relatively high, combined with a daily dose of amiodarone > 100 mg and body mass index ≤ 22.3 kg/m² at 69.0% (20/29), and its trend was also detected in the sensitivity analysis.</p><p><strong>Conclusion: </strong>Patients taking a daily amiodarone dose > 100 mg and with a body mass index ≤ 22.3 kg/m² warrant TDM implementation for MDEA to minimize the risk of MDEA-induced tissue toxicity.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"402-411"},"PeriodicalIF":0.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751651","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":"Chronic myeloid leukemia in an ulcerative colitis patient receiving azathioprine: A case report.","authors":"Asma Mensi, Nouha Trad, Raoudha Mansouri, Wiem Ayed, Emna BelHadj Mabrouk, Yosra Said, Radhouane Debbeche","doi":"10.5414/CP204603","DOIUrl":"10.5414/CP204603","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a chronic inflammatory bowel disease usually treated by azathioprine. It is a well-established risk factor for colorectal cancers and extraintestinal malignancies. Nevertheless, the risk of myeloid leukemia in patients with UC is less known. We report a case of a 51-year-old patient, with a history of extensive ulcerative colitis, who was treated with azathioprine at a dose of 2.5 mg/kg/day. Seven years later, he presented an increased count of white blood cells at 25,400/μL and of platelets at 1,382,000/μL. Peripheral blood smear showed 1% blasts and 20% myelemia. The karyotype showed the Philadelphia chromosome and the RT-PCR revealed the BCR-ABL transcript. Thus, chronic myeloid leukemia (CML) was confirmed and imatinib was prescribed. This case reported a rare and serious event in a UC patient and illustrates the importance of closely monitoring this population.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"423-426"},"PeriodicalIF":0.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751652","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}