{"title":"Drug repositioning: examining antipsychotic drugs and their anticancer effects.","authors":"Aysen Sagnak, Ferda Ari","doi":"10.1007/s40199-025-00562-1","DOIUrl":"10.1007/s40199-025-00562-1","url":null,"abstract":"<p><p>Cancer leads the list of causes of death worldwide, and the search for new and rapid treatment options for this disease has accelerated. New chemotherapeutic agents that inhibit tumor growth and proliferation are being introduced to the market; however, it presents various challenges, including the lengthy effectiveness of clinical trials, difficulty transitioning to phase 3 clinical stages, and high financial costs. A drug that had previously gained popularity in the market, has recently been repositioned for a different purpose, making it an excellent target for the treatment of several diseases. This review specifically focuses on the anti-cancer effects of repositioned antipsychotic medications that were studied for cancer treatment as well as their combination studies with other chemotherapeutic agents, using a literature search. A literature review covering the last 15 years was conducted using the PubMed (MEDLINE), Google Scholar, and Web of Science databases, with the keywords 'anticancer,' 'antipsychotic drugs,' and 'drug repurposing' used in combination. Studies that yielded productive results across broad historical ranges were included in the review. Initially, the correlation between schizophrenia patients and cancer was explored. Next, antipsychotic drugs with reported anticancer activities were identified, and their in vitro and in vivo anticancer mechanisms were revealed. Finally, the potential contributions and significance of these drugs in future therapeutic approaches were highlighted. In conclusion our literature search has revealed that antipsychotic medications can be useful in treating cancer.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 2","pages":"24"},"PeriodicalIF":2.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658650","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}
Mohammad Shafiei, Mohammad Ali Faramarzi, Somayeh Mojtabavi
{"title":"From code to cure: AI-Driven innovation in monoclonal antibody development.","authors":"Mohammad Shafiei, Mohammad Ali Faramarzi, Somayeh Mojtabavi","doi":"10.1007/s40199-025-00567-w","DOIUrl":"10.1007/s40199-025-00567-w","url":null,"abstract":"","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 2","pages":"23"},"PeriodicalIF":2.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636476","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":"Efficacy of dostarlimab in recurrent or advanced mismatch Repair-Deficient endometrial Cancer as a Single-Agent therapy: A systematic review and Meta-Analysis.","authors":"Ramazan Rezaei, Hedieh Haji Khodaverdi Khani","doi":"10.1007/s40199-025-00564-z","DOIUrl":"10.1007/s40199-025-00564-z","url":null,"abstract":"<p><strong>Background: </strong>The effectiveness of PD-1 inhibitors for treating endometrial cancer (EC) remains a topic of debate. Guidelines lack consistency regarding the preferred treatments for advanced cases, as well as for patients experiencing metastasis or recurrence. Thus, our goal was to assess the efficacy of Dostarlimab, a PD-1 inhibitor, in EC by incorporating data from clinical trials to create a more comprehensive database.</p><p><strong>Methods: </strong>We conducted a thorough and systematic search of the Scopus, Medline, Embase, and Web of Science databases, identifying all eligible studies on Dostarlimab's efficacy in endometrial cancer.</p><p><strong>Results: </strong>Our data demonstrated that the hazard ratio of OS in the pooled proportion of participants was 43%. The hazard ratio of PFS in the pooled proportion of EC patients was 0.39 (95% CI: 0.31-0.49). The overall analysis generated a probability of remaining in response of 72.71% (95% CI: 60.94-84.49%). In addition, pooling the results from both subgroups of EC patients, including proficient mismatch repair (pMMR) and deficient mismatch repair (dMMR), yielded an ORR of 33.93% (95% CI: 21.49-46.37%) and a DCR of 51.73% (95% CI: 37.0-66.42%). Overall, the deficient mismatch repair group compared to the proficient mismatch repair group showed better outcomes. Finally, the dMMR subgroup showed a median PFS of 7.86 months (95% CI: 4.46-11.26).</p><p><strong>Conclusion: </strong>Dostarlimab demonstrated limited efficacy in patients with pMMR EC, but it represented better outcomes in those with dMMR EC.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 2","pages":"22"},"PeriodicalIF":2.5,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567257","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":"Glucocorticoid withdrawal syndrome: Disproportionality analysis of cases using VigiBase data.","authors":"Lütfi Mangal, Burcu Eda Arda, Hande Sipahi","doi":"10.1007/s40199-025-00565-y","DOIUrl":"10.1007/s40199-025-00565-y","url":null,"abstract":"<p><strong>Background: </strong>Glucocorticoids are associated with withdrawal syndrome, but specific glucocorticoid types that cause severe conditions remain unclear.</p><p><strong>Objectives: </strong>This study identified glucocorticoids that exhibit significant pharmacovigilance signals for withdrawal, directly comparing the different types to determine those that exhibit a higher risk. We also aimed to investigate the routes of administration for glucocorticoids that are most likely to cause glucocorticoid withdrawal syndrome (GWS) and identify the age, sex, and regional groups among which GWS is more common.</p><p><strong>Methods: </strong>We extracted the region, severity, age group, sex, and indications from VigiBase reports on GWS from January 2013 to December 2023.</p><p><strong>Results: </strong>Among 343,296 adverse drug reactions, 1,713 were withdrawal syndrome, with a higher prevalence among females (60%). Prednisone accounted for 28% of the cases, followed by hydrocortisone (17%) and betamethasone (14%). Case numbers tended to peak in 2021, with the highest incidence between ages 18-44 (36%) and significant regional variations for different glucocorticoids. Most cases (77%) were serious, with 18% requiring prolonged hospitalization. Predominant administration routes were topical for betamethasone, triamcinolone, and hydrocortisone; oral for prednisone and prednisolone; and intravenous for methylprednisolone. Disproportionality signals indicated that hydrocortisone exhibited the highest association with GWS (reporting odds ratio [ROR]: 4.04, 95% confidence interval [CI]: 3.59-4.53), followed by betamethasone (ROR: 3.81, 95% CI: 3.35-4.32), triamcinolone (ROR: 2.15, 95% CI: 1.83-2.52), and cortisone (ROR: 1.57, 95% CI: 0.99-2.50).</p><p><strong>Conclusion: </strong>Abrupt withdrawal of glucocorticoid therapy may cause GWS. Healthcare providers should inform patients about the potential risks of withdrawal, particularly when prescribing topical hydrocortisone and betamethasone, topical and nasal triamcinolone, and oral and topical cortisone, to promote safer practices.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 2","pages":"21"},"PeriodicalIF":2.5,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559476","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}
Maria J Moura, André D Pereira, Daniel J F Santos, Ana G Silva, Carla C A D Paiva, Belmiro P M Duarte
{"title":"Cleaning validation in pharmaceutical quality control laboratories: a structured protocol for contamination risk mitigation.","authors":"Maria J Moura, André D Pereira, Daniel J F Santos, Ana G Silva, Carla C A D Paiva, Belmiro P M Duarte","doi":"10.1007/s40199-025-00566-x","DOIUrl":"10.1007/s40199-025-00566-x","url":null,"abstract":"<p><strong>Background: </strong>Cleaning activities are critical in pharmaceutical manufacturing to prevent cross-contamination of Active Pharmaceutical Ingredients (APIs). Traditionally, cleaning validation protocols have focused on production lines. However, there is a growing trend toward extending these protocols to Quality Control (QC) laboratories, encompassing both glassware and stainless-steel equipment.</p><p><strong>Objectives: </strong>This paper presents a systematic approach for developing cleaning validation protocols specifically designed for QC laboratory equipment, aimed at improving cleaning effectiveness and ensuring regulatory compliance.</p><p><strong>Methods: </strong>The proposed methodology includes: (i) identifying the worst-case API; (ii) performing recovery studies to optimize sampling methods and solvent selection; and (iii) employing statistical tools such as descriptive analysis and hypothesis testing to refine the protocol in line with current industry standards.</p><p><strong>Results: </strong>A case study involving Oxcarbazepine demonstrates the application of the proposed protocol, evaluating surface contamination across various QC instruments and assessing detergent residues to validate cleaning effectiveness.</p><p><strong>Conclusion: </strong>The proposed strategy provides a structured, statistically grounded framework for developing cleaning validation protocols in QC laboratories, promoting effective contamination control and adherence to regulatory standards.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 2","pages":"20"},"PeriodicalIF":2.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552553","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":"Profiling metoprolol enantiomers in urine of hypertensive patients.","authors":"Behrouz Seyfinejad, Kimiya Jouyban, Jalil Houshyar, Amirreza Jabbaripour Sarmadian, Abolghasem Jouyban","doi":"10.1007/s40199-025-00563-0","DOIUrl":"10.1007/s40199-025-00563-0","url":null,"abstract":"<p><strong>Background: </strong>Metoprolol, a widely used β-blocker, is administered as a racemic mixture, with (S)-metoprolol being more pharmacologically active. Its metabolism by CYP2D6 exhibits significant inter-individual variability due to genetic polymorphisms. While enantioselective pharmacokinetics have been studied in single-dose trials, data on long-term therapy in hypertensive patients is limited. This study examines urinary enantiomer profiles to assess variability in metabolism and excretion.</p><p><strong>Objectives: </strong>This study investigates the enantiomeric profile of metoprolol in urine samples collected from hypertensive patients receiving long-term racemic metoprolol therapy. The research aims to improve the analytical performance of the method to explore the enantioselective metabolism and excretion of the drug, focusing on the variation in enantiomer ratios among patients and the potential implications for clinical practice.</p><p><strong>Methods: </strong>Urine samples were collected from 30 hypertensive patients treated with racemic metoprolol. The samples were analyzed using capillary electrophoresis (CE) with clarithromycin as a chiral selector. Prior to CE analysis, liquid-liquid extraction was performed to isolate metoprolol from urine. The CE method employed an online preconcentration method and had a detection limit of 0.015 µg mL<sup>-1</sup> for each enantiomer, a linear range of 0.05 to 2.0 µg mL<sup>-1</sup>, and demonstrated intra-day and inter-day precision below 6.3%, with accuracy within 5.6%.</p><p><strong>Results: </strong>Metoprolol enantiomers were quantified in patients' urine samples, with enantiomer ratios varying among individuals. The enantiomer ratio (S/R) exceeded 1 in most patients, reflecting higher (S)-metoprolol concentrations. However, in approximately 40% of patients, the ratio was less than 1, suggesting possible enantioselective renal excretion.</p><p><strong>Conclusion: </strong>The study confirms that there is substantial inter-individual variability in the enantioselective metabolism and excretion of metoprolol among hypertensive patients. The findings emphasize the need to consider enantioselective pharmacokinetics in clinical practice, especially for chiral drugs like metoprolol. The results also suggest that the duration of treatment may affect the metabolism and excretion of enantiomers, warranting further investigation into the effects of long-term drug administration on enantiomeric ratios.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 2","pages":"19"},"PeriodicalIF":2.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552554","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}
Muhammad Shoaib, Hira Arif, Asia Naz Awan, Moona Mehboob Khan, Sehrish Batool, Shakil Ahmed
{"title":"Synthesis and optimization of fluoxetine-loaded polymeric nanoparticles for dual therapeutic applications in cancer and depression.","authors":"Muhammad Shoaib, Hira Arif, Asia Naz Awan, Moona Mehboob Khan, Sehrish Batool, Shakil Ahmed","doi":"10.1007/s40199-025-00561-2","DOIUrl":"10.1007/s40199-025-00561-2","url":null,"abstract":"<p><strong>Background: </strong>Fluoxetine, an antidepressant, has shown potential anticancer effects. However, its therapeutic efficacy is limited by its poor bioavailability and rapid metabolism. Nanotechnology is advancing medicine, particularly in developing suitable drug delivery systems to improve therapeutic effects and reduce drug side effects.</p><p><strong>Objectives: </strong>This study aims to synthesize chemically conjugated fluoxetine-dextran nanoparticles (FLX-DEX NPs) to improve the pharmacokinetic profile in plasma and brain to improve antidepressant and anticancer activity against glioma and breast cancer. Besides this, it also targets to reduce the side effects of the drug via delivering the payload to pathological cells.</p><p><strong>Methods: </strong>Fluoxetine was conjugated to aldehyde-functionalized dextran to give pH stimulus release from its nanoparticles. The spectral and morphological characterization was performed using dynamic light scattering (DLS), atomic force microscopy (AFM), UV, FTIR and <sup>1</sup>HNMR. The stability was determined using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) to evaluate thermal stability and phase transitions of the fluoxetine-dextran nanoparticles. Non-compartmental model was employed to compare the pharmacokinetics of FLX and its nanoparticles in the plasma and various parts of Sprague-Dawley rats. Furthermore, the in vitro safety profile, cytotoxic activity on MCF-7 breast cancer and U87 glioma cell lines and antidepressant effects were measured using various animal models. The levels of dopamine and serotonin in brain were monitored after a fortnight treatment of FLX and its NPs.</p><p><strong>Results: </strong>The nanoparticles were found to be round to slightly elliptical, having size less than 50 nm and charge -15-20 mV. These nanoparticles were more stable to the drug as depicted by thermoanalysis. The particles showed a controlled and pH stimuli released. The C<sub>max</sub>, T<sub>max</sub>, t<sub>1/2</sub>, volume of distribution and plasma elimination values were 5.23, 2, 15 h, 1.94 and 0.045, respectively, on oral administration of 30 mg/ kg/day. They passed 20% and 18% viability against MCF-7 and glioma cancer at 10 mg/kg/day dose without retarding its anti-depressant effect.</p><p><strong>Conclusion: </strong>FLX-DEX NPs offer dual therapeutic benefits, enhancing anticancer activity and antidepressant effects. The extended half-life and controlled fluoxetine release improved the pharmacokinetics and therapeutic outcomes, suggesting a promising nanotechnology-based approach for cancer and depression treatment.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 2","pages":"18"},"PeriodicalIF":2.5,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215203","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":"Stearyl amine tailored spanlastics embedded within tetronic<sup>®</sup> nanogel for boosting the repurposed anticancer potential of mebendazole: formulation, in vitro profiling, cytotoxicity assessment, and in vivo permeation analysis.","authors":"Mai El Halawany, Marwa Sharaky, Diana Aziz","doi":"10.1007/s40199-025-00560-3","DOIUrl":"10.1007/s40199-025-00560-3","url":null,"abstract":"<p><strong>Background: </strong>Mebendazole (MBZ) is an anthelmintic drug that was repurposed as an anti-cancer agent.</p><p><strong>Objectives: </strong>This study aimed at formulating MBZ into stearylamine tailored spanlastics dispersed in nanogel for enhancing MBZ anti-tumor efficacy against skin cancer.</p><p><strong>Methods: </strong>MBZ spanlastics were prepared by thin film hydration using 2<sup>1</sup> × 3<sup>1</sup> factorial design. The formulation variables were the total amount (mg) of Span 60 and Tween 80 in the formulations and the ratio between Span 60 and Tween 80.</p><p><strong>Results: </strong>Optimal spanlastics formulation was composed of 400 mg of Span 60 and Tween 80 in a ratio of 2:1 and showed EE% of 78 ± 2.9% and PS of 284.00 ± 35.36 nm. Stearylamine (20 mg) was added to the optimized formulation and showed acceptable positive charge (zeta potential = 47.53 ± 1.50 mV). It was dispersed in 30% Tetronic<sup>®</sup>1107 solution to form a nanogel. MBZ nanogel was assessed for their cytotoxic effect on cell proliferation against human malignant melanoma and epidermoid carcinoma cell lines and showed 38.70 ± 1.70% and 48.60 ± 0.50% (respectively) cell proliferation compared to the control group (100%). Finally, its permeation through Wistar rat skin was tested.</p><p><strong>Conclusion: </strong>SA-spanlastics nanogel holds potential as an effective nanocarrier for boosting MBZ anti-cancer efficacy.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 1","pages":"17"},"PeriodicalIF":2.5,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742402","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":"The impact of Rosa dmascena Mill. on gastrointestinal disorders: a comprehensive analysis through clinical trials, systematic review, and meta-analysis.","authors":"Nader Behgam, Sobhan Rahimi Esbo, Hossein-Ali Nikbakht, Maedeh Rezghi, Zahra Memariani","doi":"10.1007/s40199-025-00558-x","DOIUrl":"10.1007/s40199-025-00558-x","url":null,"abstract":"<p><strong>Objectives: </strong>Rosa damascena Mill. has been studied in clinical trials for the treatment of diverse gastrointestinal diseases. The aim of this study is to conduct a systematic review and meta-analysis of clinical trials using R. damascena in the management of gastrointestinal disorders.</p><p><strong>Evidence acquisition: </strong>PubMed, Web of Science, Embase, Scopus, and Google Scholar were searched up to Jun 30, 2024. Clinical trials utilizing R. damascena for gastrointestinal disorders were included in the study. The study protocol was registered in PROSPERO (CRD42024519644). The main keywords for the search were R. damascena, gastrointestinal, digestive system, and clinical trials. The Cochrane RoB 2.0 tool was employed for quality assessment of randomized controlled trials. A summary of intervention effects for each study was provided by calculating standardized mean differences and accompanying 95% confidence intervals using a random-effects model. Weighted mean differences and heterogeneity between studies were assessed using Hedges's method and Cochran's Q test, respectively. Additionally, the risk ratio (RR) index was utilized to investigate the effect of R. damascena.</p><p><strong>Results: </strong>Thirteen studies were included for systematic review. The results showed that the use of R. damascena significantly improves the Quality of life (SMD: 0.84, CI95%: 0.03 to 1.65, P = 0.041) and mean defecation frequency per week (SMD: 0.86, CI95%:0.14 to 1.58, P = 0.018) in patients with constipation. However, no improvement was observed in the Bristol stool form scale in patients with constipation, and this relationship was not statistically significant either (SMD: -1.34, CI95%: -4.39 to 1.71, P = 0.388). Also, the rate of incomplete evacuation significantly improved in patients with constipation (RR: 0.78, CI95%: 0.63 to 0.94, P = 0.035).</p><p><strong>Conclusion: </strong>Based on the results of this study, R. damascena could have promising effects on symptoms of patients with functional constipation and their quality of life. Future studies should focus on standardizing methodologies, exploring different dosage levels, and investigating its effects on a wider range of gastrointestinal conditions.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"33 1","pages":"16"},"PeriodicalIF":2.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669379","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}