Pharmacology Research & Perspectives最新文献

{"title":"Correction to \"Pros and cons for statins use and risk of Parkinson's disease: An updated perspective\".","authors":"","doi":"10.1002/prp2.1221","DOIUrl":"10.1002/prp2.1221","url":null,"abstract":"","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11156577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284428","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":"Long-lasting, biochemically modified mRNA, and its frameshifted recombinant spike proteins in human tissues and circulation after COVID-19 vaccination.","authors":"László G Boros, Anthony M Kyriakopoulos, Carlo Brogna, Marina Piscopo, Peter A McCullough, Stephanie Seneff","doi":"10.1002/prp2.1218","DOIUrl":"10.1002/prp2.1218","url":null,"abstract":"<p><p>According to the CDC, both Pfizer and Moderna COVID-19 vaccines contain nucleoside-modified messenger RNA (mRNA) encoding the viral spike glycoprotein of severe acute respiratory syndrome caused by corona virus (SARS-CoV-2), administered via intramuscular injections. Despite their worldwide use, very little is known about how nucleoside modifications in mRNA sequences affect their breakdown, transcription and protein synthesis. It was hoped that resident and circulating immune cells attracted to the injection site make copies of the spike protein while the injected mRNA degrades within a few days. It was also originally estimated that recombinant spike proteins generated by mRNA vaccines would persist in the body for a few weeks. In reality, clinical studies now report that modified SARS-CoV-2 mRNA routinely persist up to a month from injection and can be detected in cardiac and skeletal muscle at sites of inflammation and fibrosis, while the recombinant spike protein may persist a little over half a year in blood. Vaccination with 1-methylΨ (pseudouridine enriched) mRNA can elicit cellular immunity to peptide antigens produced by +1 ribosomal frameshifting in major histocompatibility complex-diverse people. The translation of 1-methylΨ mRNA using liquid chromatography tandem mass spectrometry identified nine peptides derived from the mRNA +1 frame. These products impact on off-target host T cell immunity that include increased production of new B cell antigens with far reaching clinical consequences. As an example, a highly significant increase in heart muscle 18-flourodeoxyglucose uptake was detected in vaccinated patients up to half a year (180 days). This review article focuses on medical biochemistry, proteomics and deutenomics principles that explain the persisting spike phenomenon in circulation with organ-related functional damage even in asymptomatic individuals. Proline and hydroxyproline residues emerge as prominent deuterium (heavy hydrogen) binding sites in structural proteins with robust isotopic stability that resists not only enzymatic breakdown, but virtually all (non)-enzymatic cleavage mechanisms known in chemistry.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11169277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311393","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":"Pharmacist intervention to improve adherence to medication among heart failure patients at North East Ethiopia hospital","authors":"Abate Wondesen Tsige, Tsegaye Ababiya Kotiso, Kassahun Dires Ayenew, Siraye Genzeb Ayele","doi":"10.1002/prp2.1199","DOIUrl":"https://doi.org/10.1002/prp2.1199","url":null,"abstract":"Heart failure (HF) is a major and growing medical problem and its management is still challenging due to the coexistence of complications, co‐morbidity, and medication non‐adherence. HF patients who are adherent to their medication have fewer HF exacerbations, improved survival, and lower healthcare expenditure. Adherence to HF medication plays a pivotal role in attaining maximal therapeutic outcomes. The aim was to assess the medication adherence of heart failure patients at Debre Berhan Comprehensive Specialized Hospital (DBCSH). A pre‐post interventional study was undertaken from July 1, 2022, to December 31, 2022, at the medical referral clinic of DBCSH. The educational interventions were provided for 6 months. Medication adherence was determined using the Morisky Green Levin Medication Adherence Scale (MGLS). The data was entered into Epidata version 4.2.0 and analyzed using SPSS version 25.0 statistical software. Descriptive statistics and binary logistic regression analysis were performed. The strength of the association between predictor variables and outcome variables was determined using a 95% confidence interval and adjusted odd ratio. In the pre‐intervention phase, 54.6% of patients had medium medication adherence, while in the post‐intervention phase, 36.4% of patients had high medication adherence and 61.9% of patients had medium medication adherence. Following the intervention, medication cost (120, 50%), inadequate availability of drugs (75, 31%), and forgetfulness (30, 13%) were the main reasons for medication non‐adherence. The presence of co‐morbidity and the number of co‐morbidity (<jats:italic>p</jats:italic> &lt; .05) were significantly associated with the occurrence of decreased medication adherence in the pre‐intervention phase. Interventions by pharmacists to educate HF patients about the nature of their disease and providing brochures to increase awareness of their medications have been shown to improve medication adherence.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140830174","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":"Prediction of cell cycle distribution after drug exposure by high content imaging analysis using low‐toxic DNA staining dye","authors":"Kazuma Takeuchi, Yumiko Nishimura, Takayoshi Matsubara, Sho Isoyama, Asuka Suzuki, Masaaki Matsuura, Shingo Dan","doi":"10.1002/prp2.1203","DOIUrl":"https://doi.org/10.1002/prp2.1203","url":null,"abstract":"Interference in cell cycle progression has been noted as one of the important properties of anticancer drugs. In this study, we developed the cell cycle prediction model using high‐content imaging data of recipient cells after drug exposure and DNA‐staining with a low‐toxic DNA dye, SiR‐DNA. For this purpose, we exploited HeLa and MCF7 cells introduced with a fluorescent ubiquitination‐based cell cycle indicator (Fucci). Fucci‐expressing cancer cells were subjected to high‐content imaging analysis using OperettaCLS after 36‐h exposure to anticancer drugs; the nuclei were segmented, and the morphological and intensity properties of each nucleus characterized by SiR‐DNA staining were calculated using imaging analysis software, Harmony. For the use of training, we classified cells into each phase of the cell cycle using the Fucci system. Training data (<jats:italic>n</jats:italic> = 7500) and validation data (<jats:italic>n</jats:italic> = 2500) were randomly sampled and the binary classification prediction models for G1, early S, and S/G2/M phases of the cell cycle were developed using four supervised machine learning algorithms. We selected random forest as the model with the best performance through 10‐fold cross‐validation; the accuracy rate was approximately 75%–87%. Regarding feature importance, variables expected to be biologically related to the cell cycle, for example, signal intensity and nuclear size, were highly ranked, suggesting the validity of the model. These results showed that the cell cycle can be predicted in cancer cells by simply exploiting the current prediction model using fluorescent images of DNA‐staining dye, and the model could be applied for the use of future ex vivo drug sensitivity diagnosis.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140830398","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":"Pharmacogenetic variability of tuberculosis biomarkers in native and mestizo Peruvian populations","authors":"Luis Jaramillo‐Valverde, Kelly S. Levano, David D. Tarazona, Silvia Capristano, Cesar Sanchez, Julio A. Poterico, Eduardo Tarazona‐Santos, Heinner Guio","doi":"10.1002/prp2.1179","DOIUrl":"https://doi.org/10.1002/prp2.1179","url":null,"abstract":"In Peru, 29 292 people were diagnosed with tuberculosis in 2022. Although tuberculosis treatments are effective, 3.4%–13% are associated with significant adverse drug reactions, with drug‐induced liver injury (DILI) considered the most predominant. Among the first‐line antituberculosis drugs, isoniazid is the main drug responsible for the appearance of DILI. In liver, isoniazid (INH) is metabolized by N‐acetyltransferase‐2 (<jats:italic>NAT2</jats:italic>) and cytochrome P450 2E1 (<jats:italic>CYP2E1</jats:italic>). Limited information exists on genetic risk factors associated with the presence of DILI to antituberculosis drugs in Latin America, and even less is known about these factors in the native and mestizo Peruvian population. The aim of this study was to determine the prevalence of <jats:italic>NAT2</jats:italic> and <jats:italic>CYP2E1</jats:italic> genotypes in native and mestizo population. An analytical cross‐sectional analysis was performed using genetic data from mestizo population in Lima and native participants from south of Peru. <jats:italic>NAT2</jats:italic> metabolizer was determined as fast, intermediate and slow, and <jats:italic>CYP2E1</jats:italic> genotypes were classified as c1/c1, c1/c2 and c2/c2, from molecular tests and bioinformatic analyses. Of the 472 participants, 36 and 6 <jats:italic>NAT2</jats:italic> haplotypes were identified in the mestizo and native population, respectively. In mestizo population, the most frequent <jats:italic>NAT2</jats:italic>*5B and <jats:italic>NAT2</jats:italic>*7B haplotypes were associated with DILI risk; while in natives, <jats:italic>NAT2</jats:italic>*5G and <jats:italic>NAT2</jats:italic>*13A haplotypes were associated with decreased risk of DILI. For <jats:italic>CYP2E1</jats:italic>, c1/c1 and c1/c2 genotypes are the most frequent in natives and mestizos, respectively. The linkage disequilibrium of <jats:italic>NAT2</jats:italic> single nucleotide polymorphisms (SNPs) was estimated, detecting a block between all SNPs natives. In addition, a block between rs1801280 and rs1799929 for <jats:italic>NAT2</jats:italic> was detected in mestizos. Despite the limitations of a secondary study, it was possible to report associations between <jats:italic>NAT2</jats:italic> and <jats:italic>CYP2E</jats:italic> alleles with Peruvian native and mestizo by prevalence ratios. The results of this study will help the development of new therapeutic strategies for a Tuberculosis efficient control between populations.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140798729","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 pharmacology and tolerability of REC‐994, a redox‐cycling nitroxide compound, in randomized phase 1 dose‐finding studies","authors":"Ron Alfa, Timothy Considine, Shafique Virani, Matt Pfeiffer, Anthony Donato, Daniel Dickerson, Diana Shuster, Joel Ellis, Kristen Rushton, Helen Wei, Christopher Gibson","doi":"10.1002/prp2.1200","DOIUrl":"https://doi.org/10.1002/prp2.1200","url":null,"abstract":"Abstract Cerebral cavernous malformation (CCM) has variable clinical symptoms, including potentially fatal hemorrhagic stroke. Treatment options are very limited, presenting a large unmet need. REC‐994 (also known as tempol), identified as a potential treatment through an unbiased drug discovery platform, is hypothesized to treat CCMs through a reduction in superoxide, a reactive oxygen species. We investigated the safety, tolerability, and pharmacokinetic profile of REC‐994 in healthy volunteers. Single‐ and multiple‐ascending dose (SAD and MAD, respectively) studies were conducted in adult volunteers (ages 18–55). SAD study participants received an oral dose of REC‐994 or placebo. MAD study participants were randomized 3:1 to oral doses of REC‐994 or matching placebo, once daily for 10 days. Thirty‐two healthy volunteers participated in the SAD study and 52 in the MAD study. Systemic exposure increased in proportion to REC‐994 dose after single doses of 50–800 mg and after 10 days of dosing over the 16‐fold dose range of 50–800 mg. Median T max and mean t 1/2 were independent of dose in both studies, and the solution formulation was more rapidly absorbed. REC‐994 was well tolerated. Treatment‐emergent adverse effects across both studies were mild and transient and resolved by the end of the study. REC‐994 has a favorable safety profile and was well tolerated in single and multiple doses up to 800 mg with no dose‐limiting adverse effects identified. Data support conducting a phase 2 clinical trial in patients with symptomatic CCM.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140662456","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":"Impact of pharmaceutical care for asthma patients on health‐related outcomes: An umbrella review","authors":"Olalla Montero Pérez, Fernando Salazar González, Ernesto Sánchez Gómez, Concepción Pérez Guerrero","doi":"10.1002/prp2.1195","DOIUrl":"https://doi.org/10.1002/prp2.1195","url":null,"abstract":"Abstract Recent systematic reviews suggest that pharmacists' interventions in asthma patients have a positive impact on health‐related outcomes. Nevertheless, the association is not well established, and the role of clinical pharmacists is poorly represented. The aim of this overview of systematic reviews is to identify published systematic reviews assessing the impact of pharmacists' interventions on health‐related outcomes measured in asthma patients. PubMed, Embase, Scopus, and Cochrane Library were searched from inception to December 2022. Systematic reviews of all study designs and settings were included. Methodological quality was assessed using AMSTAR 2. Two investigators performed study selection, quality assessment and data collection independently. Nine systematic reviews met the inclusion criteria. Methodological quality was rated as high in one, low in two, and critically low in six. Reviews included 51 primary studies reporting mainly quality of life, asthma control, lung capacity, and therapeutic adherence. Only four studies were carried out in a hospital setting and only two reviews stated the inclusion of severe asthma patients. The quality of the systematic reviews was generally low, and this was the major limitation of this overview of systematic reviews. However, solid evidence supports that pharmaceutical care improves health‐related outcomes in asthma patients.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140678948","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":"Induction of hepatic CYP3A4 expression by cholesterol and cholic acid: Alterations of gene expression, microsomal activity, and pharmacokinetics","authors":"Genki Minegishi, Yuka Kobayashi, Mayu Fujikura, Ayane Sano, Yasuhiro Kazuki, Kaoru Kobayashi","doi":"10.1002/prp2.1197","DOIUrl":"https://doi.org/10.1002/prp2.1197","url":null,"abstract":"Abstract Human cytochrome P450 3A4 (CYP3A4) is a drug‐metabolizing enzyme that is abundantly expressed in the liver and intestine. It is an important issue whether compounds of interest affect the expression of CYP3A4 because more than 30% of commercially available drugs are metabolized by CYP3A4. In this study, we examined the effects of cholesterol and cholic acid on the expression level and activity of CYP3A4 in hCYP3A mice that have a human CYP3A gene cluster and show human‐like regulation of the coding genes. A normal diet (ND, CE‐2), CE‐2 with 1% cholesterol and 0.5% cholic acid (HCD) or CE‐2 with 0.5% cholic acid was given to the mice. The plasma concentrations of cholesterol, cholic acid and its metabolites in HCD mice were higher than those in ND mice. In this condition, the expression levels of hepatic CYP3A4 and the hydroxylation activities of triazolam, a typical CYP3A4 substrate, in liver microsomes of HCD mice were higher than those in liver microsomes of ND mice. Furthermore, plasma concentrations of triazolam in HCD mice were lower than those in ND mice. In conclusion, our study suggested that hepatic CYP3A4 expression and activity are influenced by the combination of cholesterol and cholic acid in vivo.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140679169","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":"Coadministration of fluconazole to boost subtherapeutic sirolimus concentrations: A case report","authors":"Camilo Scherkl, Andreas D. Meid, Sven E. Cuntz, Laura Classen, Johanna Weiss, David Czock, Walter E. Haefeli","doi":"10.1002/prp2.1198","DOIUrl":"https://doi.org/10.1002/prp2.1198","url":null,"abstract":"Individual sirolimus whole blood concentrations are highly variable, critically influenced by the concomitant use of cytochrome P450 (CYP) 3A inducers or inhibitors, and also modulated by food. Therapeutic drug monitoring is therefore recommended, especially at treatment start or in circumstances that can influence sirolimus exposure. In this case report, we highlight the challenge of achieving therapeutic sirolimus concentrations and present pragmatic solutions with regimen adaptions, pharmacokinetic enhancement (use of a drug–drug interaction), concentration monitoring, and subsequent modeling of population pharmacokinetics to support treatment decisions. In a 69‐year‐old female patient with allogeneic hematopoietic stem cell transplantation, tacrolimus concentrations were stable until she developed cerebral toxoplasmosis with tonic–clonic seizures. During treatment of this acute infection, tacrolimus concentrations dropped to subtherapeutic levels and remained largely unaffected by dose increases. Only the simultaneous administration of the CYP3A4 inhibitor fluconazole and a shortening of the sirolimus dosing intervals to a (non‐approved) twice‐daily administration led to successful control of the concentrations, which ultimately even made a dose reduction possible. This intervention resulted in an increase of sirolimus mean trough concentration to 5.85 ng/mL, i.e., into the desired target range. Additionally, a higher ratio of sirolimus trough levels/daily dose from 26.9 to 109 ng/mL/mg/kg/day was achieved with the initiation of fluconazole. Thus, this case report describes the use of clinical pharmacological concepts and pharmacokinetic modeling to optimize treatment strategies in an individual patient. This strategy could be generalized to other CYP inhibitors and other treatment regimens.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140626788","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":"Absorption and pharmacokinetics of bupivacaine after bilateral topical administration in tonsillar fossae for posttonsillectomy pain relief","authors":"Kristin Sandal Berg, Ellisiv Seines, Peter Gál, Lise Løberg‐Emanuelsen, Audun Stubhaug, Erik Waage Nielsen, Olav Spigset","doi":"10.1002/prp2.1196","DOIUrl":"https://doi.org/10.1002/prp2.1196","url":null,"abstract":"No previous studies have investigated the systemic absorption of bupivacaine when used topically for posttonsillectomy pain. The present study was undertaken to investigate the pharmacokinetics of bupivacaine after administration by a swab in the tonsillar fossae over 4 min after tonsillectomy. Eleven adult patients undergoing elective tonsillectomy were recruited. After removal of both tonsils, each of the two tonsillar fossae was covered with a swab moistened with 2 mL of bupivacaine 5 mg/mL, that is, a total of 20 mg bupivacaine. Blood samples were drawn after 0, 5, 10, 20, 30, 45, and 60 min. Bupivacaine was analyzed with an ultra‐high‐performance liquid chromatography–tandem mass spectrometry method. The highest single measured bupivacaine serum concentration was 23.2 ng/mL and took place 10 min after drug administration. Mean (±SD) C<jats:sub>max</jats:sub> was 11.4 ± 6.0 ng/mL and mean t<jats:sub>max</jats:sub> was 11.3 ± 4.7 min. Mean t<jats:sub>1/2</jats:sub> was 31.6 ± 9.3 min. As the toxic concentration threshold has been reported to be in the interval 1500–4500 ng/mL, the concentrations measured were well below 2% of the lowest cited toxic threshold. In conclusion, this study shows that applying 4 mL of bupivacaine 5 mg/mL by a swab in the tonsillar fossae posttonsillectomy yields very low plasma concentrations, suggesting its safe application without any risk of systemic toxic effects.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140565236","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}