Cancer Chemotherapy and Pharmacology最新文献

{"title":"Chronic treatment with carboplatin induces mechanical hypersensitivity and neurochemical changes in the mouse dorsal root ganglia and spinal cord.","authors":"Arisai Martínez-Martínez, Lizeth Yazmin Ponce-Gomez, Juan Antonio Vazquez-Mora, Laura Yanneth Ramírez-Quintanilla, Héctor Fabián Torres-Rodríguez, Christopher M Peters, Juan Miguel Jiménez-Andrade","doi":"10.1007/s00280-025-04815-3","DOIUrl":"https://doi.org/10.1007/s00280-025-04815-3","url":null,"abstract":"<p><strong>Purpose: </strong>Carboplatin is a widely used antineoplastic drug, but it is associated with severe adverse effects, including peripheral neuropathy. However, the neurobiological mechanisms underlying this side effect are not fully known. Thus, we determined neurochemical changes in the lumbar dorsal root ganglia (DRG) and spinal cord following carboplatin treatment.</p><p><strong>Methods: </strong>Male BALB/c (23 weeks-old) mice received carboplatin (i.p.; 60 mg/kg/week for 4 weeks) or vehicle. Hindpaw mechanical sensitivity was evaluated at baseline and after carboplatin administration. On day 30 post-first carboplatin administration, mice were euthanized, and the lumbar spinal cord and DRG were processed for immunohistochemistry. Within the L4 DRG, we determined the percentage of neurons expressing the neuropeptide CGRP and the cell injury marker ATF3. Macrophage (CD68, CD163), and blood vessel density (endomucin) were also determined in the DRG. In the spinal cord, we examined the expression of several neuropeptides (CGRP, galanin, NPY) and a marker for astrocyte activation (GFAP).</p><p><strong>Results: </strong>Carboplatin-treated mice displayed hindpaw mechanical hypersensitivity. The percentage of DRG neurons expressing CGRP and ATF3 as well as the density of CD68⁺ macrophages were significantly greater in carboplatin- compared to vehicle-treated mice. Conversely, the density of CD163⁺ macrophages was significantly reduced in carboplatin- compared to vehicle-treated mice. In the spinal dorsal horn, carboplatin-treated mice showed significantly greater CGRP, galanin, and NPY expression than vehicle-treated mice. There were no changes in the density of endomucin⁺ blood vessels and GFAP immunoreactivity between groups in the DRG and spinal cord, respectively.</p><p><strong>Conclusion: </strong>Carboplatin induced several neurochemical changes in the mouse DRG and spinal cord, which may contribute to the development of carboplatin-induced peripheral neuropathy.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"90"},"PeriodicalIF":2.3,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124334","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 analysis of fluorouracil and oxaliplatin in the absence or presence of zolbetuximab in locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.","authors":"Akihiro Yamada, Jianning Yang, Peter L Bonate, Nakyo Heo, Srinivasu Poondru","doi":"10.1007/s00280-025-04808-2","DOIUrl":"10.1007/s00280-025-04808-2","url":null,"abstract":"<p><strong>Purpose: </strong>Zolbetuximab, a monoclonal antibody targeting claudin 18.2 (CLDN18.2), is approved in combination with chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative, CLDN18.2-positive, unresectable, advanced or recurrent gastric cancer (in Japan) and in combination with fluoropyrimidine- and platinum-containing chemotherapy for first-line locally advanced unresectable or metastatic HER2-negative, CLDN18.2-positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (in geographies including but not limited to the US, Europe, and China). Noncompartmental analysis (NCA) was previously used to evaluate the effect of zolbetuximab on pharmacokinetics (PK) of 5-fluorouracil (5-FU) and oxaliplatin; however, limitations of NCA confounded the results. This study utilized population pharmacokinetic (PopPK) analysis to address these limitations.</p><p><strong>Methods: </strong>In Cohort 2 of the phase 2 ILUSTRO study (NCT03505320), patients with locally advanced unresectable or metastatic HER2-negative, CLDN18.2-positive G/GEJ adenocarcinoma received zolbetuximab with modified folinic acid, 5-FU, and oxaliplatin. PopPK models were developed to evaluate the impact of zolbetuximab on PK of 5-FU and oxaliplatin (including simultaneous analysis of free and total platinum).</p><p><strong>Results: </strong>PK of 5-FU was adequately described by a 1-compartment model with zero-order input and first-order elimination. PK of free and total platinum was simultaneously described by a 3-compartment model with zero-order input, first-order elimination, and time-dependent free fraction. No impact of zolbetuximab on 5-FU PK or on systemic clearance or free fraction of oxaliplatin in plasma was observed. The effect of zolbetuximab on oxaliplatin distribution volume (12.3% decrease) was statistically significant but not considered clinically relevant.</p><p><strong>Conclusion: </strong>PopPK analysis suggests no effect of zolbetuximab on 5-FU or oxaliplatin PK.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"89"},"PeriodicalIF":2.3,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084622","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":"Effect of plasma exchange on tirabrutinib plasma concentration in a patient with lymphoplasmacytic lymphoma: A case report.","authors":"Takuya Araki, Akiko Kaneta, Hisashi Takei, Nobuhiko Kobayashi, Hideaki Yashima, Junko Tsukamoto, Yuri Miyazawa, Yoshiyuki Ogawa, Hiroshi Handa, Koujirou Yamamoto","doi":"10.1007/s00280-025-04812-6","DOIUrl":"https://doi.org/10.1007/s00280-025-04812-6","url":null,"abstract":"<p><strong>Purpose: </strong>Tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, is used to treat lymphoplasmacytic lymphoma (LPL). A hallmark complication of LPL is hyperviscosity syndrome (HVS), caused by markedly elevated serum IgM levels. Plasma exchange (PE) is a standard treatment for HVS but may also remove circulating drugs, particularly those with high protein binding, potentially reducing drug exposure and efficacy. Evaluating the impact of PE on the pharmacokinetics of drugs used to treat LPL is important for optimal treatment.</p><p><strong>Methods: </strong>We report the case of a 63-year-old man with LPL who presented with acute headache and was diagnosed with HVS. Tirabrutinib (480 mg, once daily) was initiated, and PE was performed the next day because of persistent IgM elevation. To assess the impact of PE on tirabrutinib plasma concentrations, blood samples were collected approximately 3 h prior to PE (C15), immediately before PE (C18), and immediately after PE (C20).</p><p><strong>Results: </strong>The concentrations at C15, C18 and C20 were 33.3, 16.9, and 11.4 ng/mL, respectively. The elimination rate constant (ke) was calculated as 0.226 h⁻¹ before PE and 0.197 h⁻¹ during PE. Based on the pre-PE ke, the predicted post-PE concentration (C20) assuming no PE was approximately 10.6 ng/mL, slightly lower than the observed value.</p><p><strong>Conclusion: </strong>PE appeared to have minimal impact on the tirabrutinib plasma concentration, likely due to its large volume of distribution. Although further cases are needed, this case supports the feasibility of concomitant PE during tirabrutinib therapy without significant compromise of drug efficacy.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"88"},"PeriodicalIF":2.3,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074469","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 therapeutic applications of talazoparib: a comprehensive review.","authors":"Saphal Lakshmi Pasupulati, Katiboina Srinivasa Rao, Sushil Sharma, C Madhavrao, Gaurav Rangari, Arup Kumar Misra, L V Simhachalam Kutikuppala, T Devika, Sandhya Rani Sarikonda","doi":"10.1007/s00280-025-04810-8","DOIUrl":"https://doi.org/10.1007/s00280-025-04810-8","url":null,"abstract":"","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"87"},"PeriodicalIF":2.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069315","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":"Anlotinib in cancer therapy: mechanisms of action, clinical applications, and future perspectives.","authors":"Jianhua Ding, Chai Hong Yeong, Lei Wang, Chunyan Shi, Long Li, Lijun Song, Wenxiu Ma, Peng Li","doi":"10.1007/s00280-025-04811-7","DOIUrl":"https://doi.org/10.1007/s00280-025-04811-7","url":null,"abstract":"","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"86"},"PeriodicalIF":2.3,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051693","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":"RNA processing kinase inhibitors and epigenetic inhibitors in combination with oncology drugs or investigational agents in multi-cell type patient-derived tumor cell line spheroids.","authors":"Beverly A Teicher, Thomas S Dexheimer, Thomas Silvers, Nathan P Coussens, Eric Jones, Steven D Gore, Mark Kunkel, James H Doroshow","doi":"10.1007/s00280-025-04800-w","DOIUrl":"10.1007/s00280-025-04800-w","url":null,"abstract":"<p><strong>Purpose: </strong>The alternative splicing of mRNA precursors allows one gene to yield multiple proteins with distinct functions. CDC-like kinases serve as pivotal regulators of alternative splicing. Control of protein expression also occurs at the level of DNA through histone methylation and demethylation. We investigated the activity of two CLK inhibitors, cirtuvivint and CC-671, and the LSD1 inhibitor iadademstat alone and in combination with anticancer drugs or investigational agents.</p><p><strong>Methods: </strong>Well-characterized patient-derived cancer cell lines from the PDMR ( https://pdmr.cancer.gov/models/database.htm ) were used along with standard human cancer cell lines. Multi-cell type-tumor spheroids were grown from a ratio of 6:2.5:1.5 malignant cells, endothelial cells, and mesenchymal stem cells. Following three days of growth, the spheroids were exposed to the single agents or combinations at concentrations up to the clinical C_max value for each agent, if known. After seven days of exposure, cell viability was assessed using the CellTiter-Glo 3D assay and spheroid volume was assessed by bright field imaging.</p><p><strong>Results: </strong>Several of the targeted oncology drugs exhibited additive and greater-than-additive cytotoxicity when combined with a CLK inhibitor, or the LSD1 inhibitor. These agents included the XPO1 inhibitor, eltanexor, and the KRAS G12D specific inhibitor MRTX-1133 which had activity in tumor lines harboring the KRAS G12D mutation. LSD1 inhibition was effective with ubiquitin proteasome pathway inhibitors.</p><p><strong>Conclusion: </strong>These findings may provide guidance for development of clinical trial combination regimens including cirtuvivint, CC-671 or iadademstat. Full data sets are available on PubChem.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"85"},"PeriodicalIF":2.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12431893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039206","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":"A novel cardioprotective mechanism of rosuvastatin: restoring PINK1/parkin-mediated mitophagy via SIRT1/FOXO1 activation in doxorubicin-induced cardiotoxicity.","authors":"Yomna S Momen, Mohamed A Kandeil, Mohamed O Mahmoud","doi":"10.1007/s00280-025-04805-5","DOIUrl":"https://doi.org/10.1007/s00280-025-04805-5","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy remains a key cancer treatment despite advancements in cancer therapy, with doxorubicin (DOX) widely used for solid and hematological tumors. However, its clinical use is limited by severe acute and chronic cardiotoxicity, primarily driven by oxidative stress and mitophagic dysregulation. Rosuvastatin (RSV), a lipid-lowering drug, has shown cardioprotective effects. This study aimed to investigate the molecular mechanism underlying RSV's protection against DOX-induced cardiotoxicity.</p><p><strong>Methods: </strong>Adult male Wistar rats were assigned to eight groups: control, RSV-only (20 mg/kg, orally, for 3 weeks), DOX-only (18 mg/kg, intraperitoneally, over 2 weeks), RSV + DOX, CQ + RSV + DOX (chloroquine 25 mg/kg, intraperitoneally, for 2 weeks), CQ-only, RSV + CQ, and CQ + DOX. 48 h after the last DOX injection, serum myocardial injury markers, oxidative stress markers, and autophagic flux biomarkers (LC3II & P62) were assessed. RT-PCR evaluated lncRNA APF gene expression, while western blotting quantified p-SIRT1, FOXO1, p-PINK1, and p-Parkin protein levels.</p><p><strong>Results: </strong>RSV mitigated DOX-induced myocardial injury and oxidative stress while restoring autophagic flux, as evidenced by P62 and LC3II reversal. RSV enhanced lncRNA APF gene expression, p-SIRT1, p-PINK1, and p-Parkin levels while downregulating FOXO1. The autophagy inhibitor CQ blunted RSV's cardioprotective effects.</p><p><strong>Conclusion: </strong>RSV protects against DOX-induced cardiotoxicity, at least in part, by restoring autophagic flux and rescuing PINK1/Parkin-mediated mitophagy via upregulation of the SIRT1/FOXO1 pathway. Thus, combining RSV with DOX may enable patients to complete chemotherapy with a reduced risk of cardiotoxicity. However, further studies are warranted to confirm its translational potential.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"84"},"PeriodicalIF":2.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944032","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":"Exposure-response analysis of asciminib efficacy and safety in patients with chronic myelogenous leukemia in chronic phase.","authors":"Sherwin K B Sy, Yiqun Yang, Christelle Darstein, Deok Yong Yoon, Kohinoor Dasgupta, Shruti Kapoor, Shengyuan Wu, Yasunori Kawakita, Matthias Hoch, Kai Grosch","doi":"10.1007/s00280-025-04806-4","DOIUrl":"https://doi.org/10.1007/s00280-025-04806-4","url":null,"abstract":"","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"83"},"PeriodicalIF":2.3,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944045","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":"Biotransformation and disposition of C¹⁴-labeled sonrotoclax ([¹⁴C]BGB-11417) in preclinical safety species and characterization of unique contribution from gut microbiome.","authors":"Tingting Cai, Dan Su, Zhiyu Tang, Jianmei Liu, Wei Tang, Yue Wu, Fan Wang","doi":"10.1007/s00280-025-04803-7","DOIUrl":"https://doi.org/10.1007/s00280-025-04803-7","url":null,"abstract":"<p><strong>Introduction: </strong>Sonrotoclax (BGB-11417), a second-generation B-cell lymphoma-2 (BCL-2) inhibitor currently in clinical development, requires comprehensive verification of its biotransformation and disposition profiles in safety species.</p><p><strong>Methods: </strong>[¹⁴C]BGB-11417 was employed to assess its pharmacokinetics, excretion, tissue distribution and metabolite profiles in mice and dogs. Radioactivity in plasma and excreta were analyzed to determine pharmacokinetics and mass balance. The metabolite profiles were generated by the chromatographic separation coupled with radioactivity detector/ mass spectrometry. Quantitative whole-body autoradiography (QWBA) was performed to assess tissue distribution in both pigmented or albino mice. Anaerobic human fecal incubation was conducted to evaluate the biotransformation contribution of gut microbiome.</p><p><strong>Results: </strong>T_max of [¹⁴C]BGB-11417 radioactivity was observed at 4 h, with a T_1/2 ranging 6.5-7.2 h in both species. The highest tissue exposure was noted in metabolic and excretory organs, with 90% of the administered radioactivity eliminated through mouse excreta within 48 h. Prolonged excretion kinetics accompanied by marked inter-individual variability were observed in dog excreta. A distinct nitro-reduction pathway was detected exclusively in dogs. These metabolites were also detected in anaerobic incubations of [¹⁴C]BGB-11417 with human feces. Aerobic incubation of the nitro-reduction metabolite with dog feces directly yielded lipid-conjugated products, confirming that conjugation occurs spontaneously post-reduction rather than on the parent drug.</p><p><strong>Conclusion: </strong>The concordance between dog fecal metabolites and human fecal incubations underscored cross-species gut microbiome similarities. These findings offer a mechanistic insight into the fate of sonrotoclax in organisms and guide the interpretation of metabolic clearance in human.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"82"},"PeriodicalIF":2.3,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943989","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 thymine-challenge test to prospectively evaluate dihydropyrimidine dehydrogenase activity for risk of severe 5-fluorouracil-induced gastrointestinal toxicity.","authors":"Nuala Helsby, Katrina Sharples, Yu Jin Kim, David Porter, Kathryn Burns, Soo Hee Jeong, Sarah Benge, Sanjeev Deva, Ben Lawrence, Christopher Jackson, Richard North, R Matthew Strother, John Duley, Michael Findlay","doi":"10.1007/s00280-025-04804-6","DOIUrl":"10.1007/s00280-025-04804-6","url":null,"abstract":"<p><strong>Purpose: </strong>Inherited dihydropyrimidine dehydrogenase (DPD) deficiency is a risk factor for severe 5-fluorouracil toxicity. We report a phenotyping approach (thymine challenge test) to prospectively determine DPD activity and the association with severe adverse events.</p><p><strong>Methods: </strong>The primary aim of this prospective study was to determine whether a thymine challenge test could prospectively identify patients at risk of severe toxicity from treatment with 5-fluorouracil/capecitabine in combination chemotherapy schedules or monotherapy. The focus was prediction of those at risk of ≥ grade 3 gastrointestinal toxicity. DPD activity was determined from the thymine/dihydrothymine (THY/DHT) ratio measured in a urine sample after a thymine test dose (250 mg, oral).</p><p><strong>Results: </strong>Of the 166 patients, 11.7% had severe diarrhoea/mucositis. The THY/DHT ratio was not significantly different in these individuals compared to those with minimal toxicity. However, post hoc analysis found decreased DPD activity in those who had non-gastrointestinal toxicity, most notably grade ≥ 2 Hand-Foot syndrome (p = 0.001).</p><p><strong>Conclusion: </strong>The data do not support our primary hypothesis that this phenotyping approach would discriminate those at risk of severe/life-threatening gastrointestinal toxicity. The clinical factors which influence gastrointestinal toxicity, particularly in patients receiving CAPOX require further investigation.</p><p><strong>Clinical trial registration: </strong>ACTRN 12,617,001,109,392 registered 28/07/2017.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"81"},"PeriodicalIF":2.3,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12361283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871635","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}