Investigational New Drugs最新文献

{"title":"Phase II trial of multi-tyrosine kinase inhibitor ESK981 in combination with PD-1 inhibitor nivolumab in patients with metastatic castration-resistant prostate cancer.","authors":"Elisabeth I Heath, Wei Chen, Jae E Choi, Kimberlee Dobson, Melanie Smith, Tomasz Maj, Ilona Kryczek, Weiping Zou, Arul M Chinnaiyan, Yuanyuan Qiao","doi":"10.1007/s10637-024-01482-8","DOIUrl":"10.1007/s10637-024-01482-8","url":null,"abstract":"<p><p>Increasing the response rates of immune checkpoint inhibitors in patients with metastatic castration-resistant prostate cancer (mCRPC) presents a significant challenge. ESK981 is a multi-tyrosine kinase and PIKfyve lipid kinase inhibitor that augments immunotherapeutic responses. In this phase II study, ESK981 was combined with the PD-1 blocking monoclonal antibody nivolumab to test for potentially improved response rates in patients with mCRPC who have progressed on androgen receptor (AR)-targeted agents and chemotherapy. Eligible patients received ESK981 orally once daily for five consecutive days, followed by a two-day break. Patients were also treated with nivolumab intravenously on Day 1 of each 28-day cycle. The primary endpoints were a 50% reduction in prostate-specific antigen (PSA50), and safety. Secondary endpoints included radiographic progression free survival (rPFS) and overall survival (OS). Additional investigations included whole exome sequencing in patients. Ten patients were enrolled. The maximum PSA decline from baseline of 14% was achieved in only one patient. Grade 3 treatment-related adverse events (AEs) included fatigue, anemia, and lymphopenia. There were no Grade 4 events. The median rPFS was 3.7 months (95% CI, 1.6-8.4). The median OS was 9.6 months (95% CI, 1.8-22.4). The study was terminated due to futility after 10 patients. Whole exome sequencing identified AR amplification in 63% of patients (5/8). ESK981 + nivolumab showed no antitumor activity in patients with AR-positive (AR+) mCRPC. Further evaluation of ESK981 combined with the PD-1 inhibitor nivolumab in AR + mCRPC patients is not warranted. (Trial registration: ClinicalTrials.gov NCT04159896. Registration date: November 12, 2019.).</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"675-684"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gremlin1: a BMP antagonist with therapeutic potential in Oncology.","authors":"Zhao Jin, Yanshuo Cao","doi":"10.1007/s10637-024-01474-8","DOIUrl":"10.1007/s10637-024-01474-8","url":null,"abstract":"<p><p>Gremlins, originating from early 20th-century Western folklore, are mythical creatures known for causing mechanical malfunctions and electronic failures, aptly dubbed \"little devils\". Analogously, GREM1 acts like a horde of these mischievous entities by antagonizing the bone morphogenetic protein (BMP signaling) pathway or through other non-BMP dependent mechanisms (such as binding to Fibroblast Growth Factor Receptor 1and Epidermal Growth Factor Receptor) contributing to the malignant progression of various cancers. The overexpression of GREM1 promotes tumor cell growth and survival, enhances angiogenesis within the tumor microenvironment, and creates favorable conditions for tumor development and dissemination. Consequently, inhibiting the activity of GREM1 or blocking its interaction with BMP presents a promising strategy for suppressing tumor growth and metastasis. However, the role of GREM1 in cancer remains a subject of debate, with evidence suggesting both oncogenic and tumor-suppressive functions. Currently, several pharmaceutical companies are researching the GREM1 target, with some advancing to Phase I/II clinical trials. This article will provide a detailed overview of the GREM1 target and explore its potential role in cancer therapy.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"716-727"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics, treatment, and outcomes of pembrolizumab-induced uveitis.","authors":"Zhaoquan Wu, Wei Sun, Chunjiang Wang","doi":"10.1007/s10637-024-01464-w","DOIUrl":"10.1007/s10637-024-01464-w","url":null,"abstract":"<p><p>Pembrolizumab has been associated with episodes of uveitis, and the clinical characteristics between them are unknown. The aim of this study was to investigate the clinical characteristics of pembrolizumab-induced uveitis and to provide reference for prevention, diagnosis and treatment. We collected studies related to pembrolizumab-induced uveitis by searching databases for retrospective analysis until April 30, 2024. The median age of the 31 patients was 63 years (range 7, 82), and the median duration of uveitis onset was 12 weeks (range 0.4, 108). Decreased vision (41.9%) and blurred vision (25.8%) were the most common complaints. Uveitis can be manifested as Vogt-Koyanagi-Harada disease-like uveitis (22.6%) and Birdshot uveitis (6.5%). Uveitis mainly affects both eyes and is related to anterior uveitis (35.5%), panuveitis (25.8%) and posterior uveitis (19.4%). Patients receiving topical steroid drops, systemic steroids, and withdrawal of pembrolizumab significantly improved symptoms at a median time of 4 weeks (range 2, 16). The possibility of uveitis should be considered when patients are treated with pembrolizumab and experience eye symptoms such as blurred vision and decreased vision. Depending on the severity of uveitis, treatment with topical and systemic steroids may be selected.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"510-517"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-marketing safety concerns with relugolix: a disproportionality analysis of the FDA adverse event reporting system.","authors":"Chunyong Xia, Zhijing Liu, Jie Liu, Li Lin, Maohua Chen","doi":"10.1007/s10637-024-01457-9","DOIUrl":"10.1007/s10637-024-01457-9","url":null,"abstract":"<p><strong>Background: </strong>Relugolix has been used to treat advanced prostate cancer. This study assessed adverse events (AEs) associated with relugolix from the US Food and Drug Administration Adverse Event Reporting System (FAERS).</p><p><strong>Methods: </strong>Disproportionality analysis, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed to quantify the signals of relugolix-associated AEs.</p><p><strong>Results: </strong>A total of 5,059,213 reports of AEs were collected from the FAERS database, of which 5,662 reports were identified with relugolix as the \"primary suspect (PS)\". A total of 70 significant disproportionality PTs conforming to the four algorithms were simultaneously retained. Unexpected new AEs, such as erectile dysfunction, gynaecomastia, testicular atrophy, male genital atrophy, libido decreased might also occur.</p><p><strong>Conclusion: </strong>This study found potential new AEs signals and might provide important support for clinical monitoring and risk identification of relugolix.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"500-509"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: The kinesin Eg5 inhibitor K858 induces apoptosis but also survivin-related chemoresistance in breast cancer cells.","authors":"Francesca De Iuliis, Ludovica Taglieri, Gerardo Salerno, Anna Giuffrida, Bernardina Milana, Sabrina Giantulli, Simone Carradori, Ida Silvestri, Susanna Scarpa","doi":"10.1007/s10637-024-01469-5","DOIUrl":"10.1007/s10637-024-01469-5","url":null,"abstract":"","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"601"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase II trial of multi-kinase inhibitor ESK981 in patients with metastatic castration-resistant prostate cancer.","authors":"Elisabeth I Heath, Wei Chen, Lance Heilbrun, Jae E Choi, Kimberlee Dobson, Melanie Smith, Tomasz Maj, Ulka Vaishampayan, Ilona Kryczek, Weiping Zou, Arul M Chinnaiyan, Yuanyuan Qiao","doi":"10.1007/s10637-024-01463-x","DOIUrl":"10.1007/s10637-024-01463-x","url":null,"abstract":"<p><p>ESK981 is a potent tyrosine kinase and PIKfyve lipid kinase inhibitor. This phase II trial evaluated the efficacy of ESK981 as a single agent in patients with androgen receptor-positive (AR +) metastatic castration-resistant prostate cancer (mCRPC). Eligible patients had mCRPC with progression on AR-targeted agents and without prior chemotherapy treatment. Each patient received 160 mg ESK981 once daily for 5 days per week for 4 weeks per cycle (except for an adverse event (AE) occurrence). The primary endpoints were a 50% reduction in prostate-specific antigen (PSA50), and safety. Secondary endpoints included the time and the duration of PSA response, PSA progression rates, PSA progression free survival (PFS) and overall survival (OS). Exploratory investigations included whole exome sequencing in patients before treatment, and morphological evaluation of biopsy samples pre- and post-treatment. PSA was evaluated in 13 patients. Only one patient (7.7% two-sided 95% Wilson CI (0.4%, 33.3%)) experienced a reduction in their PSA levels by 50% or more. The most common grade 3 treatment-related AEs were cardiac disorders, diarrhea, hypertension, alanine transaminase and aspartate transaminase elevations. No grade 4-5 events occurred. Median PFS was 1.8 months, and median OS was 12.1 months. Peripheral immune cells showed increased T cell activation and cytokine production in two patients who received 12-weeks of ESK981. Although relatively well tolerated, ESK981 alone showed no anti-tumor activity in patients with AR + mCRPC and its further evaluation as a single agent in AR + mCRPC is not warranted. (Trial registration: ClinicalTrials.gov, NCT03456804. Registration date: March 7, 2018).</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"566-574"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A randomized phase 1 study of safety, tolerability, and pharmacokinetics of MK-1088, a novel dual adenosine receptor antagonist, in healthy adult participants.","authors":"Pranav Gupta, Manash Chatterjee, Yeonil Kim, Kathleen Deschamps, Lieselotte Lemoine, Kristien Van Dyck, Catherine Zhou Matthews, Sylvie Rottey, Aubrey Stoch, Eseng Lai","doi":"10.1007/s10637-024-01462-y","DOIUrl":"10.1007/s10637-024-01462-y","url":null,"abstract":"<p><p>This phase 1 first-in-human study evaluated the safety, tolerability, and pharmacokinetics of MK-1088, a novel, small-molecule dual inhibitor of adenosine A_2A and A_2B receptors. Healthy adult participants were enrolled in two panels (n = 8 each) and randomly assigned to receive MK-1088 (n = 6) or placebo (n = 2) orally in each of five treatment periods. Participants in panel A received single ascending doses of MK-1088 at 1, 10, 50, and 150 mg or placebo in a fasted or fed (50 mg only) state. Participants in panel B received MK-1088 at 3, 25, 100, and 224 mg or placebo in a fasted state. Primary objectives were to evaluate safety, tolerability, and plasma pharmacokinetics following a single dose of MK-1088. The secondary objective was to evaluate the effects of a high-fat meal on pharmacokinetics. All participants (n = 16) completed the study (median age: 33 years [range: 20-43]; all were male). Treatment-related adverse events (AEs) occurred in 1 of 6 (17%), 4 of 6 (67%), 4 of 6 (67%), and 2 of 6 (33%) participants after receiving MK-1088 at 3, 25, 100, and 224 mg, respectively. No serious AEs or deaths due to any cause occurred. MK-1088 was rapidly absorbed after a single dose; half-life was ~ 11 h in the 100-224 mg dose range. The target concentration at 12 h (> 0.3 µM) was exceeded at the 50-mg dose level. MK-1088 plasma pharmacokinetics increased dose proportionately. A high-fat meal did not significantly affect pharmacokinetics at the 50-mg dose. MK-1088 was well tolerated and demonstrated dose-proportional pharmacokinetic properties that were not affected by a high-fat meal.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"492-499"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depth of response and treatment outcomes of immune checkpoint inhibitor-based therapy in patients with advanced non-small cell lung cancer and high PD-L1 expression: An exploratory analysis of retrospective multicenter cohort.","authors":"Yusuke Tachibana, Kenji Morimoto, Tadaaki Yamada, Hayato Kawachi, Motohiro Tamiya, Yoshiki Negi, Yasuhiro Goto, Akira Nakao, Shinsuke Shiotsu, Keiko Tanimura, Takayuki Takeda, Asuka Okada, Taishi Harada, Koji Date, Yusuke Chihara, Isao Hasegawa, Nobuyo Tamiya, Yuki Katayama, Naoya Nishioka, Masahiro Iwasaku, Shinsaku Tokuda, Takashi Kijima, Koichi Takayama","doi":"10.1007/s10637-024-01467-7","DOIUrl":"10.1007/s10637-024-01467-7","url":null,"abstract":"<p><p>The association between depth of response (DpR) and treatment outcomes has been documented across various types of cancer. Immune checkpoint inhibitor (ICI)-based treatment is globally used as first-line treatment for non-small cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1) expression ≥ 50%. However, in this population, the significance of DpR is not elucidated. Patients with advanced NSCLC and PD-L1 expression ≥ 50% who received ICI-monotherapy or ICI plus chemotherapy were retrospectively enrolled into this study. Treatment responses were grouped into DpR 'quartiles' by percentage of maximal tumor reduction (Q1 = 1-25%, Q2 = 26-50%, Q3 = 51-75%, and Q4 =  ≥ 76%), and no tumor reduction (NTR). The association between DpR and survival rates were determined using hazard ratios (HR) generated by the Cox proportional hazards model. The Kaplan-Meier method was used to determine survival outcomes. A total of 349 patients were included, of which 214 and 135 patients received pembrolizumab monotherapy and ICI plus chemotherapy, respectively, as first-line treatments. The majority of the patients were male. All DpR quartiles, especially Q4, showed an association with progression-free survival (PFS)/overall survival (OS). In the Q4 cohort, patients who received pembrolizumab had a longer PFS than those who received ICI plus chemotherapy. High DpR was associated with longer PFS and OS, with a more pronounced effect observed with pembrolizumab monotherapy than with ICI plus chemotherapy.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"538-546"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting multiple receptor tyrosine kinases with sitravatinib: A Phase 1b study in advanced renal cell carcinoma and castrate-resistant prostate cancer.","authors":"Shubham Pant, Byoung Chul Cho, Christos E Kyriakopoulos, Alexander Spira, Nizar Tannir, Theresa L Werner, Xiaohong Yan, Saskia Neuteboom, Richard Chao, Sanjay Goel","doi":"10.1007/s10637-024-01465-9","DOIUrl":"10.1007/s10637-024-01465-9","url":null,"abstract":"<p><p>Sitravatinib (MGCD516) is an oral inhibitor of several closely related oncogenic tyrosine kinase receptors that include VEGFR-2 (vascular endothelial growth factor receptor-2), AXL, and MET (mesenchymal-epithelial transition). The safety and antitumor activity of sitravatinib are reported in patients from two histologic cohorts (anti-angiogenesis-refractory clear cell renal cell carcinoma [RCC] and castrate-resistant prostate cancer [CRPC] with bone metastases) who participated in a Phase 1/1b study. The patients were enrolled using a 3-stage design that was based on observed objective responses. Objective response rate (ORR) was the primary endpoint. Duration of response, progression-free survival (PFS), overall survival (OS), and safety were also assessed. Overall, 48 patients (RCC n = 38, CRPC n = 10) received ≥ 1 dose of sitravatinib. Both cohorts were heavily pretreated (median number of prior systemic therapies: RCC cohort 3, CRPC cohort 6). In the RCC cohort, ORR was 25.9%, P = 0.015 (null hypothesis [ORR ≤ 10%] was rejected). Responses were durable (median duration 13.2 months). Median PFS was 9.5 months and median OS was 30.0 months. No objective responses were seen in the CRPC cohort; median PFS and OS were 5.8 months and 10.1 months, respectively. Across both cohorts, diarrhea (72.9%), fatigue (54.2%), and hypertension (52.1%) were the most frequent all-cause treatment-emergent adverse events (TEAEs). Diarrhea and vomiting (both, 6.3%) were the most frequent serious TEAEs considered related to study treatment. Sitravatinib demonstrated an acceptable safety profile and promising clinical activity in patients with clear cell RCC refractory to prior angiogenesis inhibitor therapy. Strong indicators for clinical activity were not seen in patients with CRPC and bone metastases. Clinical trial registration:ClinicalTrials.gov NCT02219711.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"547-558"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design optimization of Fucoidan-coating Cationic Liposomes for enhance Gemcitabine delivery.","authors":"Epiphane K Silli, Zhenjiang Zheng, Xintao Zhou, Mengfei Li, Jiali Tang, Ruizhe Guo, Chunlu Tan, Ying Wang","doi":"10.1007/s10637-024-01455-x","DOIUrl":"10.1007/s10637-024-01455-x","url":null,"abstract":"<p><p>Obstacles facing chemotherapeutic drugs for cancers led scientists to load Gemcitabine (GEM) into nanocarriers like liposomes, known for their nontoxicity profile and targeting capacity. The liposomal nanostructures containing GEM were coated with Fucoidan (FU) due to its anti-tumor properties by targeting cancer cells. Thus four different cationic liposomes formulations were prepared by thin-film hydration method in optimal conditions: DOTAP (formulation A); DPPC/DOTAP (4:1 molar ratio, formulation B), DPPC/DMPC/DOTAP (4:1:1 molar ratio, formulation C) and DPPC/DMPC/DOTAP/DSPE-mPEG2000 (4:1:1:0.1 molar ratio, formulation D). They were studied to identify lipid-compositions offering effective GEM-entrapment and successful coating of FU on the liposome surface. Additional qualitative characteristics, such as particle size, polydispersity index, zeta potential, stability and in vitro drug release were then evaluated. Formulation C gave the best GEM-entrapment efficiency (EE) but formed aggregates when coated with FU, giving non-homogenous large size particles then not suitable for effective delivery. It was the same situation with formulation A and B. Only the formulation D showed a good GEM-EE (> 80%) and affinity by successful coating FU from three different algae species. The PEGylated formulation D coated of FU, with regard to storage stability and drug release studies, revealed to be a promising approach on design of optimal drug delivery system.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"518-530"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}