Pub Date : 2024-01-01DOI: 10.2174/1574892818666230607093231
Zhiyuan Luo, Yangchao Chen
mRNA emerged as an attractive therapy modality with the development of mRNA structure engineering techniques and delivery platforms. mRNA therapeutics, applied for vaccine therapy, protein replacement therapy, and chimeric antigen receptor (CAR) T cell-based therapy, has shown huge potential in treating a wide range of diseases, such as cancer and rare genetic diseases, with successful and exciting preclinical and clinical progress. In mRNA therapeutics, a potent delivery system is key to the success of its application for disease treatment. Herein, different types of mRNA delivery strategies, including nanoparticles produced from lipid or polymer materials, virus-based platforms, and exosome-based platforms, are mainly focused.
{"title":"Unlocking Delivery Strategies for mRNA Therapeutics.","authors":"Zhiyuan Luo, Yangchao Chen","doi":"10.2174/1574892818666230607093231","DOIUrl":"10.2174/1574892818666230607093231","url":null,"abstract":"<p><p>mRNA emerged as an attractive therapy modality with the development of mRNA structure engineering techniques and delivery platforms. mRNA therapeutics, applied for vaccine therapy, protein replacement therapy, and chimeric antigen receptor (CAR) T cell-based therapy, has shown huge potential in treating a wide range of diseases, such as cancer and rare genetic diseases, with successful and exciting preclinical and clinical progress. In mRNA therapeutics, a potent delivery system is key to the success of its application for disease treatment. Herein, different types of mRNA delivery strategies, including nanoparticles produced from lipid or polymer materials, virus-based platforms, and exosome-based platforms, are mainly focused.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"126-129"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9947777","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}
Pub Date : 2024-01-01DOI: 10.2174/1574892818666230330105016
Sadegh Paydari Rostami, Negar Moghare Dehkordi, Yazdan Asgari, Mohammad Reza Bolouri, Nasrin Shayanfar, Reza Falak, Gholam Ali Kardar
Background: Epithelial-to-mesenchymal transition (EMT) plays a role in the invasion and metastasis of cancer cells. During this phenomenon, Snail can promote tumor progression by upregulating mesenchymal factors and downregulating the expression of pro-apoptotic proteins.
Objective: Therefore, interventions on the expression rate of Snails may show beneficial therapeutic applications.
Methods: In this study, the C-terminal region of Snail1, capable of binding to E-box genomic sequences, was subcloned into the pAAV-IRES-EGFP backbone to make complete AAV-CSnail viral particles. B16F10 as a metastatic melanoma cell line, with a null expression of wild type TP53 was transduced by AAV-CSnail. Moreover, the transduced cells were analyzed for in vitro expression of apoptosis, migration, and EMT-related genes, and in vivo inhibition of metastasis.
Results: In more than 80% of the AAV-CSnail transduced cells, the CSnail gene expression competitively reduced the wild-type Snail functionality and consequently lowered the mRNA expression level of EMT-related genes. Furthermore, the transcription level of cell cycle inhibitory factor p21 and pro-apoptotic factors were promoted. The scratch test showed a decrease in the migration ability of AAV-CSnail transduced group compared to control. Finally, metastasis of cancer cells to lung tissue in the AAV-CSnail-treated B16F10 melanoma mouse model was significantly reduced, pointing out to prevention of EMT by the competitive inhibitory effect of CSnail on Snail1 and increased apoptosis of B16F10 cells.
Conclusion: The capability of this successful competition in reducing the growth, invasion, and metastasis of melanoma cells indicates that gene therapy is a promising strategy for the control of the growth and metastasis of cancer cells.
{"title":"Competitive Effect of Overexpressed C-terminal of Snail-1 (CSnail) in Control of the Growth and Metastasis of Melanoma Cells.","authors":"Sadegh Paydari Rostami, Negar Moghare Dehkordi, Yazdan Asgari, Mohammad Reza Bolouri, Nasrin Shayanfar, Reza Falak, Gholam Ali Kardar","doi":"10.2174/1574892818666230330105016","DOIUrl":"10.2174/1574892818666230330105016","url":null,"abstract":"<p><strong>Background: </strong>Epithelial-to-mesenchymal transition (EMT) plays a role in the invasion and metastasis of cancer cells. During this phenomenon, Snail can promote tumor progression by upregulating mesenchymal factors and downregulating the expression of pro-apoptotic proteins.</p><p><strong>Objective: </strong>Therefore, interventions on the expression rate of Snails may show beneficial therapeutic applications.</p><p><strong>Methods: </strong>In this study, the C-terminal region of Snail1, capable of binding to E-box genomic sequences, was subcloned into the pAAV-IRES-EGFP backbone to make complete AAV-CSnail viral particles. B16F10 as a metastatic melanoma cell line, with a null expression of wild type TP53 was transduced by AAV-CSnail. Moreover, the transduced cells were analyzed for in vitro expression of apoptosis, migration, and EMT-related genes, and in vivo inhibition of metastasis.</p><p><strong>Results: </strong>In more than 80% of the AAV-CSnail transduced cells, the CSnail gene expression competitively reduced the wild-type Snail functionality and consequently lowered the mRNA expression level of EMT-related genes. Furthermore, the transcription level of cell cycle inhibitory factor p21 and pro-apoptotic factors were promoted. The scratch test showed a decrease in the migration ability of AAV-CSnail transduced group compared to control. Finally, metastasis of cancer cells to lung tissue in the AAV-CSnail-treated B16F10 melanoma mouse model was significantly reduced, pointing out to prevention of EMT by the competitive inhibitory effect of CSnail on Snail1 and increased apoptosis of B16F10 cells.</p><p><strong>Conclusion: </strong>The capability of this successful competition in reducing the growth, invasion, and metastasis of melanoma cells indicates that gene therapy is a promising strategy for the control of the growth and metastasis of cancer cells.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"342-353"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9233840","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}
Background: Terminalia chebula (T. chebula) comprising chebulinic acid as its principle active constituent is used to cure various diseases. T. chebula and chebulinic acid are used as antimicrobial, antioxidant, antidiabetic, anti-inflammatory, hepatoprotective, antimutagenic, radioprotective, cardioprotective, antiproliferative, antiarthritic, anticaries, and so on.
Objective: The objective of this current study is to give an overview of the recent literature and patents of T. chebula and chebulinic acid including methods of its isolation/extraction and their application in the prevention of various cancers and other diseases.
Methods: Present research and patents highlighting the anti-cancer potential of T. chebula and chebulinic acid have been studied and discussed keeping in view the scientific novelty and impact.
Results: Both T. chebula and chebulinic acid are currently being explored for their anticancer potential in vitro and in vivo. They are either incorporated alone or in combination with other plants or drugs to show their activity and many clinical trials are also going on various potentials of the plant and chebulinic acid. Novel extraction techniques are also explored and patented. Efforts are being made to improve the bioavailability by developing Novel herbal drug delivery systems of the plant extract or chebulinic acid itself.
Conclusion: Anti-cancer potential of T. chebula and chebulinic acid may be well established by promising clinical trials and may open new interventions in various tumors. Clinical trials in conjunction with standard therapies are required to explore and validate the actual potential of T. chebula and chebulinic acid respectively.
{"title":"Chebulinic Acid: An Incipient Anticancer Agent.","authors":"Aashima, Mehak Rathi, Shilpi, Akash, Kamaljeet Kaur, Priyanka Kriplani, Kumar Guarve","doi":"10.2174/1574892819666230821110429","DOIUrl":"10.2174/1574892819666230821110429","url":null,"abstract":"<p><strong>Background: </strong><i>Terminalia chebula (T. chebula</i>) comprising chebulinic acid as its principle active constituent is used to cure various diseases. <i>T. chebula</i> and chebulinic acid are used as antimicrobial, antioxidant, antidiabetic, anti-inflammatory, hepatoprotective, antimutagenic, radioprotective, cardioprotective, antiproliferative, antiarthritic, anticaries, and so on.</p><p><strong>Objective: </strong>The objective of this current study is to give an overview of the recent literature and patents of <i>T. chebula</i> and chebulinic acid including methods of its isolation/extraction and their application in the prevention of various cancers and other diseases.</p><p><strong>Methods: </strong>Present research and patents highlighting the anti-cancer potential of <i>T. chebula</i> and chebulinic acid have been studied and discussed keeping in view the scientific novelty and impact.</p><p><strong>Results: </strong>Both <i>T. chebula</i> and chebulinic acid are currently being explored for their anticancer potential <i>in vitro</i> and <i>in vivo</i>. They are either incorporated alone or in combination with other plants or drugs to show their activity and many clinical trials are also going on various potentials of the plant and chebulinic acid. Novel extraction techniques are also explored and patented. Efforts are being made to improve the bioavailability by developing Novel herbal drug delivery systems of the plant extract or chebulinic acid itself.</p><p><strong>Conclusion: </strong>Anti-cancer potential of <i>T. chebula</i> and chebulinic acid may be well established by promising clinical trials and may open new interventions in various tumors. Clinical trials in conjunction with standard therapies are required to explore and validate the actual potential of T. chebula and chebulinic acid respectively.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"298-307"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10042084","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}
Pub Date : 2024-01-01DOI: 10.2174/1574892818666230213095717
Isabela Fernandes Pereira, Ana Maria Santos Oliveira, Anamaria Mendonça Santos, Denis de Melo Soares, Mairim Russo Serafini, Izabel Almeida Alves
Background: Cannabis use for tumor treatment has been explored in several areas, and its potential for tumor remission is currently being studied after the discovery of the endogenous cannabinoid.
Objective: The study aimed to conduct a critical patent review to identify and explore the latest advances and therapeutic strategies using Cannabis to treat cancer.
Methods: The research was carried out in the free and online database Espacenet, using the descriptors "cancer" and "Cannabis or cannabidiol" in the title or abstract. A total of 95 patents were identified for preliminary evaluation in the database. Six duplicate patents were excluded, 12 referring to traditional Chinese medicine and 36 with a title in disagreement with the scope of this review. In addition the final selection involved 21 patents that were in line with the objective of the study.
Results: As observed in the reading of patents, the interest of pharmaceutical industries and researchers and the development of new products to fight cancer have increased in recent years. The main cannabinoids present in the patents are tetrahydrocannabinol, cannabidiol, and hemp. Moreover, the patents were classified and the main applicant countries were the United States followed by Japan, with a higher filing rate in 2019 and, mainly by the industry.
Conclusion: In conclusion we can say that, the importance of parliamentary approval in the cultivation and investments that, in addition to bringing innovation to the industrial sector, enriches research in the area, contributing to the creation of new medicines.
{"title":"A Descriptive Review of <i>Cannabis sativa</i> Patents for Cancer Treatment.","authors":"Isabela Fernandes Pereira, Ana Maria Santos Oliveira, Anamaria Mendonça Santos, Denis de Melo Soares, Mairim Russo Serafini, Izabel Almeida Alves","doi":"10.2174/1574892818666230213095717","DOIUrl":"10.2174/1574892818666230213095717","url":null,"abstract":"<p><strong>Background: </strong><i>Cannabis</i> use for tumor treatment has been explored in several areas, and its potential for tumor remission is currently being studied after the discovery of the endogenous cannabinoid.</p><p><strong>Objective: </strong>The study aimed to conduct a critical patent review to identify and explore the latest advances and therapeutic strategies using <i>Cannabis</i> to treat cancer.</p><p><strong>Methods: </strong>The research was carried out in the free and online database Espacenet, using the descriptors \"cancer\" and \"<i>Cannabis</i> or cannabidiol\" in the title or abstract. A total of 95 patents were identified for preliminary evaluation in the database. Six duplicate patents were excluded, 12 referring to traditional Chinese medicine and 36 with a title in disagreement with the scope of this review. In addition the final selection involved 21 patents that were in line with the objective of the study.</p><p><strong>Results: </strong>As observed in the reading of patents, the interest of pharmaceutical industries and researchers and the development of new products to fight cancer have increased in recent years. The main cannabinoids present in the patents are tetrahydrocannabinol, cannabidiol, and hemp. Moreover, the patents were classified and the main applicant countries were the United States followed by Japan, with a higher filing rate in 2019 and, mainly by the industry.</p><p><strong>Conclusion: </strong>In conclusion we can say that, the importance of parliamentary approval in the cultivation and investments that, in addition to bringing innovation to the industrial sector, enriches research in the area, contributing to the creation of new medicines.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"137-145"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10716828","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}
Pub Date : 2023-11-01DOI: 10.2174/157489281804230217112618
{"title":"Acknowledgement To Reviewers","authors":"","doi":"10.2174/157489281804230217112618","DOIUrl":"https://doi.org/10.2174/157489281804230217112618","url":null,"abstract":"","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"33 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136103237","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}
Pub Date : 2023-11-01DOI: 10.2174/157489281804230217112506
{"title":"Patent Selections","authors":"","doi":"10.2174/157489281804230217112506","DOIUrl":"https://doi.org/10.2174/157489281804230217112506","url":null,"abstract":"","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"64 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136102910","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}
Pub Date : 2023-08-01DOI: 10.2174/157489281803230127123426
{"title":"Patent Selections","authors":"","doi":"10.2174/157489281803230127123426","DOIUrl":"https://doi.org/10.2174/157489281803230127123426","url":null,"abstract":"","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"40 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134984312","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}
Pub Date : 2023-06-26DOI: 10.2174/1574892818666230609121409
Moshi Rao, Xiaoshun Ai, Zijian Huang
Background: The aim of two-sample Mendelian randomization (MR) with a large sample size was to explore the causal cholelithiasis impact on acute pancreatitis and pancreatic cancer.
Methods: We performed the two-sample MR analysis with two models. Publicly available summary- level information for cholelithiasis was acquired from the Genome-Wide Summary Association Studies (GWAS) of FinnGen Biobank. The inverse variance weighted (IVW) method was the main method to obtain the MR estimates. Other methods were also used as supplementary methods, including MR-Egger, maximum likelihood, MR-Robust Adjusted Profile Score (MR-RAPS), weighted median, penalised weighted median method, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) method.
Results: After the selection of genetic instrumental variables (IVs), 11 single nucleotide polymorphisms (SNPs) (Model 1) and 22 SNPs (Model 2) were used to explore the effect of cholelithiasis on acute pancreatitis, and 10 SNPs (Model 1) and 24 SNPs (Model 2) on pancreatic cancer. The findings obtained by the fixed-effect IVW method with both Model 1 and Model 2 showed that genetically predicted cholelithiasis was significantly related to the elevated acute pancreatitis risk (Model 1: OR: 1.001, 95% CI: 1.000-1.002, p <0.001; Model 2: OR: 1.001, 95% CI: 1.000-1.002, p <0.001). Moreover, cholelithiasis would also raise the pancreatic cancer risk (Model 1: OR: 1.676, 95% CI: 1.228-2.288, p = 0.001; Model 2: OR: 1.432, 95% CI: 1.116-1.839, p = 0.005).
Conclusion: Genetically predicted cholelithiasis was significantly related to the elevated risk of acute pancreatitis and pancreatic cancer. More attention should be paid to patients with cholelithiasis for the primary prevention of pancreatic-related diseases.
{"title":"The Causal Effects of Cholelithiasis on Acute Pancreatitis and Pancreatic Cancer: A Large Sample Size Mendelian Randomization Analysis.","authors":"Moshi Rao, Xiaoshun Ai, Zijian Huang","doi":"10.2174/1574892818666230609121409","DOIUrl":"https://doi.org/10.2174/1574892818666230609121409","url":null,"abstract":"<p><strong>Background: </strong>The aim of two-sample Mendelian randomization (MR) with a large sample size was to explore the causal cholelithiasis impact on acute pancreatitis and pancreatic cancer.</p><p><strong>Methods: </strong>We performed the two-sample MR analysis with two models. Publicly available summary- level information for cholelithiasis was acquired from the Genome-Wide Summary Association Studies (GWAS) of FinnGen Biobank. The inverse variance weighted (IVW) method was the main method to obtain the MR estimates. Other methods were also used as supplementary methods, including MR-Egger, maximum likelihood, MR-Robust Adjusted Profile Score (MR-RAPS), weighted median, penalised weighted median method, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) method.</p><p><strong>Results: </strong>After the selection of genetic instrumental variables (IVs), 11 single nucleotide polymorphisms (SNPs) (Model 1) and 22 SNPs (Model 2) were used to explore the effect of cholelithiasis on acute pancreatitis, and 10 SNPs (Model 1) and 24 SNPs (Model 2) on pancreatic cancer. The findings obtained by the fixed-effect IVW method with both Model 1 and Model 2 showed that genetically predicted cholelithiasis was significantly related to the elevated acute pancreatitis risk (Model 1: OR: 1.001, 95% CI: 1.000-1.002, p <0.001; Model 2: OR: 1.001, 95% CI: 1.000-1.002, p <0.001). Moreover, cholelithiasis would also raise the pancreatic cancer risk (Model 1: OR: 1.676, 95% CI: 1.228-2.288, p = 0.001; Model 2: OR: 1.432, 95% CI: 1.116-1.839, p = 0.005).</p><p><strong>Conclusion: </strong>Genetically predicted cholelithiasis was significantly related to the elevated risk of acute pancreatitis and pancreatic cancer. More attention should be paid to patients with cholelithiasis for the primary prevention of pancreatic-related diseases.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9965216","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}
Pub Date : 2023-05-01DOI: 10.2174/157489281802221028105228
V. Apostolopoulos
{"title":"Meet the Editorial Board Member","authors":"V. Apostolopoulos","doi":"10.2174/157489281802221028105228","DOIUrl":"https://doi.org/10.2174/157489281802221028105228","url":null,"abstract":"","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"1 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67994271","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}
Pub Date : 2023-05-01DOI: 10.2174/157489281802221028143545
{"title":"Patent Selections","authors":"","doi":"10.2174/157489281802221028143545","DOIUrl":"https://doi.org/10.2174/157489281802221028143545","url":null,"abstract":"","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135702917","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}