{"title":"N<sup>6</sup>-Methyladenosine Reader Protein YTHDC1 Supports Proper Mitotic Progression Partly through Regulation of TPX2-Aurora A Signaling.","authors":"Rina Michimori, Ryuzaburo Yuki, Junna Tanaka, Youhei Saito, Yuji Nakayama","doi":"10.1248/bpb.b24-00542","DOIUrl":"https://doi.org/10.1248/bpb.b24-00542","url":null,"abstract":"<p><p>Chemical modification of mRNA regulates its stability and translation efficiency. The most prevalent modification is the N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) modification. YT521-B homology domain-containing proteins (YTHDCs) are \"reader\" proteins of m<sup>6</sup>A modification and contribute to various cell functions by regulating their target m<sup>6</sup>A-containing mRNAs. Although m<sup>6</sup>A modification dynamically changes throughout the cell cycle, the role of the m<sup>6</sup>A pathway in cell division remains unclear. In this study, we found that YTHDC1, one of the YTHDCs, is important for cell division. Mitotic progression is delayed in YTHDC1-knockdown cells, and the mitotic delay is mitigated by the re-expression of wild-type YTHDC1, indicating the YTHDC1 function in mitotic progression. Time-lapse imaging analysis showed that prolonged mitotic duration caused by YTHDC1 knockdown is due to the retardation of chromosome alignment and segregation. Treatment of AZ3146, an inhibitor of the spindle assembly checkpoint (SAC), mitigates the mitotic delay in YTHDC1-knockdown cells, suggesting that YTHDC1 knockdown results in SAC activation, leading to a slowdown of mitotic progression. Furthermore, increased TPX2 protein expression and the subsequent overabundance of Aurora A at the centrosomes is partly involved in YTHDC1 knockdown-induced mitotic delay. Since YTHDC1 knockdown does not affect the TPX2 mRNA level and the inhibition of protein synthesis by cycloheximide treatment impairs the YTHDC1-knockdown effect on the TPX2 protein level, YTHDC1 may post-transcriptionally regulate the TPX2 expression. Considering that TPX2 or Aurora A overexpression causes mitotic failure, these results suggest that YTHDC1 contributes to mitotic progression partly through the precise regulation of TPX2-Aurora A signaling.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"613-621"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075768","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}
Koji Sugimura, Akihiro Daikonya, Hiroyuki Fuchino, Nobuyuki Tanaka, Fred Pitisopa, Takashi Watanabe
{"title":"Plant Inventory in the Solomon Islands, with Special Reference to Medicinal Plant Resources (4). Comparison of Dendrobium (Orchidaceae) Plant Components Using Multivariate Analysis.","authors":"Koji Sugimura, Akihiro Daikonya, Hiroyuki Fuchino, Nobuyuki Tanaka, Fred Pitisopa, Takashi Watanabe","doi":"10.1248/bpb.b24-00413","DOIUrl":"https://doi.org/10.1248/bpb.b24-00413","url":null,"abstract":"<p><p>Eight species of the genus Dendrobium were collected from the Solomon Islands. The morphological and compositional characteristics of their stems and leaves were studied and compared with two Japanese medicinal species of Dendrobium by using multivariate analysis of their components. As a result, we discovered that some types of Dendrobium plants from the Solomon Islands have a composition pattern comparable to that of the Japanese medicinal species, D. catenatum. Within the same species, distinct varieties with different compositions exist based on their locations in the Solomon Islands. Certain types also have different composition patterns depending on the stem and leaf sections. Our findings show that Dendrobium plants in the Solomon Islands have a distinct stem and leaf morphology and composition, while they also share similar compositional patterns with existing medicinal species. As a result, these plants are regarded as valuable medicinal resources with the potential to be used as novel crude drug ingredients.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"622-631"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092571","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":"Treatment of Long Coronavirus Disease in Japan: A Nationwide Study of Symptom-Associated Drug Prescriptions.","authors":"Yuka Kogure, Wataru Ando, Kyoka Sakamaki, Mitsuhiro Sugawara","doi":"10.1248/bpb.b24-00762","DOIUrl":"https://doi.org/10.1248/bpb.b24-00762","url":null,"abstract":"<p><p>Long coronavirus disease (COVID) is characterized by symptoms persisting or reappearing at least 2 months post-recovery from acute coronavirus disease 2019 (COVID-19). Although Long COVID symptoms have been widely studied, data on drug prescriptions for patients with Long COVID in Japan remain limited. Therefore, this study aimed to analyze drug utilization patterns for Long COVID treatment using a nationwide database in Japan, with the goal of providing basic data to support the establishment of standard treatments in the future. The Medical Data Vision COVID-19 dataset was used to identify patients diagnosed with Long COVID between January 15, 2020 and December 31, 2022. Symptoms and prescribed medications were extracted, and descriptive statistics were used to analyze the relationship between symptoms and drug prescriptions. Among 652016 patients with COVID-19, 3769 (0.6%) developed Long COVID. Common symptoms included fatigue, bronchial asthma-like symptoms, and insomnia. Acetaminophen was the most prescribed drug in the first month of diagnosis. Other frequently prescribed drugs included dextromethorphan, l-carbocisteine, and polaprezinc. From 3 months post-diagnosis, prescriptions for Hochu-ekki-to (a traditional Japanese herbal medicine; Kampo medicine) and polaprezinc increased, especially among patients aged 30-50 years. Long COVID in Japan is characterized by a wide range of symptoms, leading to symptom-based drug prescriptions, particularly fatigue, respiratory issues, and taste disturbances. These findings offer insights into the pharmacological management of Long COVID in Japan, highlighting the need for further research on optimal treatments in the future.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"641-649"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092736","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":"Skin Permeation of Hydrophilic Middle-to-High Molecular Weight Model Drugs from Decanoic Acid/Arginine Supramolecular Hydrogels.","authors":"Ryuichiro Mochizuki, Kohsuke Shibasaki, Kaname Hashizaki, Makiko Fujii, Hiroyuki Taguchi","doi":"10.1248/bpb.b24-00770","DOIUrl":"https://doi.org/10.1248/bpb.b24-00770","url":null,"abstract":"<p><p>Decanoic acid/arginine supramolecular hydrogels (C10/Arg) were prepared and evaluated for use as skin-application formulations to improve the skin permeation of hydrophilic middle-to-high-molecular-weight drugs. Dextran (Mw; 6000 Da [Dex]) was used to evaluate the physicochemical properties of the hydrogels, and fluorescein isothiocyanate-Dex (Mw; 4000 Da [FD4], Mw; 40000 Da [FD40]) was used as a model drug to evaluate skin permeability. The addition of 1% Dex to C10/Arg resulted in a translucent supramolecular hydrogel with a lamellar liquid crystal structure, and the addition of a low-molecular-weight model drug to this hydrogel did not significantly affect its physicochemical properties. However, the addition of middle-molecular-weight Dex (6000 Da) changed the rheological properties of the gel, strengthening its internal structure and increasing its elasticity. In vitro skin permeation experiments of model drugs released from C10/Arg gels were performed using Yucatan micropig skin. C10/Arg increased the cumulative amount of FD4 permeation by 40 times after 24 h compared to the application of aqueous FD4 solution. No skin permeation from the aqueous FD40 solution was observed, but permeation was observed following treatment of the skin sample with C10/Arg. The enhanced skin permeation of model drugs by hydrogels was largely due to the contribution of C10 in the hydrogels.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"733-743"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198242","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":"Development of Nanoparticle-Based Mucosal Drug Delivery Systems for Controlling Pharmacokinetic Behaviors.","authors":"Hideyuki Sato","doi":"10.1248/bpb.b25-00071","DOIUrl":"https://doi.org/10.1248/bpb.b25-00071","url":null,"abstract":"<p><p>The mucosal layer in various mucosal tissues acts as a barrier that protects the epithelial membrane from foreign substances. However, in the process of mucosal absorption of drugs, the mucus layer, a smart biological sieve to particles and molecules, can be an obstacle to effective drug delivery. Recently, functional nanoparticles (NPs) have attracted considerable interest in the field of biopharmaceutical science owing to their delivery potential and effectiveness. Among various pharmaceutical technologies, mucopenetrating NPs (MPP) and mucoadhesive NPs (MAP) are viable dosage options for controlling pharmacokinetic behavior by modifying drug absorption from the mucosal site. MPP and MAP can rapidly deliver encapsulated drugs to the absorption site by passing through the mucus layer and/or retaining NPs near the absorption membrane, possibly resulting in better drug delivery than that of conventional approaches. Modifying the surface properties of NPs is critical for determining their potential diffusiveness within the mucus layer owing to various types of interactions between the mucosal components and the surface of NPs. Additionally, the physiological characteristics of the mucus layer (thickness, viscosity, and turnover time) differ depending on the mucosal site. Thus, a deeper understanding of the design of NPs and the functional properties of the administration site is essential for developing mucosal drug delivery systems (mDDS) to maximize the potential of target drugs. This review summarizes the basic information and functions of the mucosal layer, highlights the recent progress in designing functional NPs for mDDS, and discusses the advantages and disadvantages of mucosal administration at major mucosal sites.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"759-768"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198243","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":"Defective Repair of G<sub>1</sub>-Phase Double-Strand Breaks in WRNIP1/Ku70 Double Knockout Cells.","authors":"Akari Yoshimura, Takuya Abe, Masayuki Seki","doi":"10.1248/bpb.b25-00072","DOIUrl":"https://doi.org/10.1248/bpb.b25-00072","url":null,"abstract":"<p><p>Werner helicase-interacting protein 1 (WRNIP1) is a member of the AAA<sup>+</sup> ATPase family and is conserved from Escherichia coli to Homo sapiens. Although a role for WRNIP1 in the S phase of the cell cycle has previously been reported, the present study demonstrates a novel function for this protein in G<sub>1</sub> phase. Deletion of WRNIP1 in non-homologous end joining (NHEJ)-deficient chicken DT40 cell lines resulted in slow growth, accumulation in G<sub>1</sub> phase, an increased population of dead cells, and accumulation of double-strand breaks (DSBs), which were indirectly evaluated by γH2AX. The data suggest that WRNIP1 prevents the generation of DSBs, executes DSB repair, and/or regulates DSB repair independently of NHEJ, particularly in G<sub>1</sub> phase. The potential molecular mechanism by which WRNIP1 functions in G<sub>1</sub> phase is discussed.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"805-811"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246248","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":"Development of a Gryllus bimaculatus-Based Assay System for Evaluating Chemically Modified siRNAs.","authors":"Taketo Inoue, Shintaro Inoue, Yuhei Nogi, Jun Tsukimoto, Noriko Saito-Tarashima, Sumihare Noji, Taro Mito, Noriaki Minakawa","doi":"10.1248/bpb.b25-00289","DOIUrl":"https://doi.org/10.1248/bpb.b25-00289","url":null,"abstract":"<p><p>Small interfering RNAs (siRNAs) hold great therapeutic promise due to their ability to selectively silence disease-associated genes. Although chemically modified siRNAs have demonstrated clinical efficacy, their development remains hindered by challenges such as stability and delivery under physiological conditions. Furthermore, in vitro screening of chemically modified siRNAs using cultured cells is cost-effective but often fails to recapitulate in vivo complexity, limiting predictive accuracy. To address this, we have developed a transfection-free siRNA evaluation platform using Gryllus bimaculatus (Gb), an insect model with natural RNA uptake capacity. We first demonstrated that 21-nucleotide siRNAs induced RNA interference upon abdominal injection under conditions of free uptake. We then generated transgenic lines harboring an EGFP reporter fused to the therapeutic siRNA target sequence and integrated into the β-actin locus via clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9-mediated knock-in. Two transgenic strains (s1 and d1) were established and validated. We compared unmodified and chemically modified siRNAs designed using enhanced stabilization chemistry (ESC), a clinically validated modification pattern incorporating 2'-O-methyl, 2'-fluoro, and phosphorothioate modifications. While ESC-modified siRNAs showed reduced activity compared to unmodified natural siRNAs in conventional cell-based assays requiring transfection reagents, they exhibited consistent gene silencing in Gb, reflecting their enhanced biochemical stability under free uptake conditions at picomole-scale doses. These results establish Gb as a scalable, cost-effective, and biologically relevant platform for evaluating therapeutic siRNAs, particularly those incorporating chemical modifications.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"941-950"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526397","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}
Kenta Tanito, Teruki Nii, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama
{"title":"Screening of Human M2 Macrophage-Specific Markers for Preparation of Humanized Inflammation-Triggering Engineered Macrophage (MacTrigger).","authors":"Kenta Tanito, Teruki Nii, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama","doi":"10.1248/bpb.b25-00112","DOIUrl":"https://doi.org/10.1248/bpb.b25-00112","url":null,"abstract":"<p><p>We previously reported the development of inflammation-triggering engineered mouse macrophages (mMacTriggers) that achieve tumor-specific release of tumor necrosis factor-α (TNF-α) in response to the promoter of Arginase 1 (Arg1), an M2-specific marker in murine macrophages. Tumor-specific TNF-α release induced acute inflammation, which recruited natural killer cells or cytotoxic T cells to attack the tumor, leading to significant antitumor effects. This strategy primarily leverages innate immunity-mediated tumor suppression, which is expected to have minimal side effects-an approach noted worldwide. However, we have one issue with preparing human macrophage-derived MacTrigger (hMacTrigger) for clinical application: the Arg1 promoter is unsuitable for human use due to the low expression of Arg1 in human macrophages. Therefore, this study aimed to identify human M2 macrophage-specific markers to replace murine Arg1 through data analysis and quantitative evaluation. From an initial selection of 30 gene candidates by data analysis, we identified 8 genes with high specificity by quantitative evaluation. Among them, 4 genes-arachidonate 15-lipoxygenase (ALOX15), sialic acid-binding immunoglobulin (Ig)-like lectin 10 (SIGLEC10), fatty acid binding protein 4 (FABP4), and C-C motif chemokine ligand 22 (CCL22)-were confirmed as M2-specific markers in human macrophages. Future research will focus on preparing hMacTrigger by constructing vectors encoding TNF-α under the control of each identified gene promoter and evaluating its anti-tumor effects and side effects in vivo. This study represents a critical step toward the clinical application of the MacTrigger strategy and advances its potential use in cancer immunotherapy.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 7","pages":"966-971"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551863","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":"Second-Generation H<sub>1</sub>-Receptor Antagonists, Mequitazine, Azelastine and Desloratadine Activate Caspase-8, Caspase-3, and Gasdermin E and Induce Cell Death Showing Pyroptotic-Like Features in Macrophages at Excessively High Concentrations.","authors":"Akane Ito, Atsushi Sawamoto, Satoshi Okuyama, Mitsunari Nakajima","doi":"10.1248/bpb.b25-00312","DOIUrl":"https://doi.org/10.1248/bpb.b25-00312","url":null,"abstract":"<p><p>Histamine H<sub>1</sub> receptor (H<sub>1</sub>R) is expressed in various cells, including neurons, smooth muscle cells, hepatocytes, T and B cells, neutrophils, dendritic cells, monocytes, and macrophages. Antagonists that target the H<sub>1</sub>R are used to relieve the symptoms of allergy and inflammation. Here, we examined the inflammation-modulating and cell death-inducing effects of 10 second-generation H<sub>1</sub>R antagonists on mouse intraperitoneal macrophages, which include ketotifen, mequitazine, azelastine, oxatomide, epinastine, bepotastine, fexofenadine, loratadine, levocetirizine, and desloratadine, to assess an anticipated adverse reaction. Three of these antagonists, namely, mequitazine, azelastine, and desloratadine, induced the secretion of interleukin-1α (IL-1α), a marker of pyroptosis and an inflammatory cytokine, from the macrophages at excessively high concentrations, while reducing the secretion of another inflammatory cytokine, IL-6. We found that the macrophages treated with the 3 antagonists showed pyroptotic-like, but not apoptotic-like, morphology and died. Western blotting analysis revealed that caspase-8, caspase-3, and gasdermin E (GSDME), but not gasdermin D, were cleaved and activated in the macrophages. These results suggest that second-generation H<sub>1</sub>R antagonists such as mequitazine, azelastine, and desloratadine induce pyroptotic-like cell death accompanied by caspase-8, caspase-3, and GSDME activation in macrophages.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 7","pages":"1031-1039"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648429","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":"An Underlying Mechanism for the Altered Hypoglycemic Effects of Nateglinide in Rats with Acute Peripheral Inflammation.","authors":"Haruka Toko, Manami Ogino, Akane Nishiwaki, Moeko Kojina, Tetsuya Aiba","doi":"10.1248/bpb.b24-00582","DOIUrl":"10.1248/bpb.b24-00582","url":null,"abstract":"<p><p>The hypoglycemic effects of nateglinide (NTG) were examined in rats with acute peripheral inflammation (API) induced by carrageenan treatment, and the mechanisms accounting for altered hypoglycemic effects were investigated. NTG was administered through the femoral vein in control and API rats, and its plasma concentration profile was characterized. The time courses of the changes in plasma glucose and insulin levels were also examined. Although the plasma concentration profile of NTG in API rats was marginally distinguishable from that in control rats, the hypoglycemic effect of NTG was more persistent in API rats than in control rats. In addition, NTG elevated the plasma level of insulin more intensely in API rats than in control rats. Then, the islets of Langerhans were procured by perfusing the pancreas with collagenase solution in control and API rats, and the pancreatic mRNA expression of preproinsulin (Ins1), as well as that of sulfonylurea receptor ABCC8 (Abcc8), were examined. As a result, the expression of preproinsulin and ABCC8 mRNA increased in API rats. These findings suggest that the hypoglycemic effect of NTG was potentiated in API rats due to increased insulin secretion in the pancreas, which was caused by enhanced preproinsulin synthesis and expression of the sulfonylurea receptor.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"51-59"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063555","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}