Genes and Environment最新文献

{"title":"Correction: Development of a DNA damage assay system using stable human hepatocytes.","authors":"Masayuki Mishima, Kazuki Izawa, Masataka Tsuda, Yuichiro Higuchi, Shotaro Uehara, Hiroshi Suemizu, Kei-Ichi Sugiyama","doi":"10.1186/s41021-026-00355-1","DOIUrl":"10.1186/s41021-026-00355-1","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"48 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343798","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":"Potential of green tea extract to suppress colorectal polyp development in patients with familial adenomatous polyposis: a double-blind, randomized controlled trial Japan Familial Adenomatous Polyposis Prevention Study (J-FAPP Study I).","authors":"Hideki Ishikawa, Michihiro Mutoh, Tetsuro Yamane, Keiji Wakabayashi, Keiji Hirata, Takeo Iwama, Tomiyo Nakamura, Naohiro Tomita, Yutaka Matsuyama","doi":"10.1186/s41021-026-00354-2","DOIUrl":"10.1186/s41021-026-00354-2","url":null,"abstract":"<p><p>BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disease that results in the development of more than 100 polyps, premalignant lesions, in the colorectum. Therefore, patients with FAP are a high-risk group for colorectal cancer (CRC). The only standard method of preventing CRC is total colectomy. Thus, alternative methods to prevent the development of CRC are desired by patients. Epidemiological and animal studies suggested that green tea and its extracts, such as (−)-epigallocatechin gallate, may have the potential to prevent cancer development. RESULTS: In the present study, we evaluated the suppressive effects of green tea extract (GTE) on suppress colorectal polyps in FAP and conducted a double-blind clinical trial. Eighty patients were randomly assigned to the GTE group (1.5 g/day for 2 years) and an equal number were assigned to the placebo group. The primary endpoint of colon polyp enlargement tended to be reduced in the GTE group compared with the placebo group, with a risk ratio of 0.43 (95% confidence interval 0.12–1.49; p = 0.16). CONCLUSIONS: Given that the risk ratio was less than 0.5 and few adverse events were observed, we believe that further research using GTE after calculating the necessary sample size is calculated on the based of this study, should be considered in a future large-scale clinical trial. </p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12958651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343839","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":"Detection of germline variants in human population chronically exposed to high level natural background radiation in Kerala coast.","authors":"Vinay Jain, Divyalakshmi Saini, Radhakrishnan Sabarinathan, Birajalaxmi Das","doi":"10.1186/s41021-026-00352-4","DOIUrl":"10.1186/s41021-026-00352-4","url":null,"abstract":"<p><strong>Background: </strong>Genetic effects due to long term exposure to low doses of ionizing radiation (LDIR) in humans are not well understood. Human population living in high level natural radiation areas (HLNRAs) of Kerala coast in India are continuously exposed to chronic LDIR emanating from monazite containing beach sand for many generations. The background radiation level in this area varies from < 1.0 to 45mGy/year. The people residing in HLNRAs sometimes receives background radiation dose which is approximately 10-40 times higher than the people living in adjacent normal level natural radiation areas (NLNRAs). This population provides a unique opportunity to identify, if present, a mutational signature due to chronic low-dose radiation exposure in humans. We have employed whole exome sequencing approach to determine germline mutational changes in the lymphocytes of healthy individuals from HLNRAs (mean background dose: 31.8 ± 5.4 mGy/year, mean age: 43.0 ± 5.9 years) and compared them with healthy individuals from NLNRAs (mean background dose: 0.9 ± 0.2 mGy/year, mean age: 43.0 ± 11.3 years).</p><p><strong>Results: </strong>Our results revealed that the overall number of single nucleotide variants (SNVs) and insertions/deletions (indels) were not significantly different in HLNRA (7744 SNVs, 880 indels) and NLNRA (7951 SNVs, 856 indels) groups. A similar number of protein affecting mutations (PAMs) were observed in HLNRA (1925) and NLNRA (2082) individuals. Interestingly, several unique SNVs were identified in both the groups. In HLNRA, unique SNVs were overrepresented in genes involved in important biological pathways such as DNA repair (EXO1, PARP2, DDB1, POLQ, LIG1), epigenetic modification (KDM5D, SETDB2, KMT2B, BRD8, SIRT1), cell cycle progression (CDK14, CCND1) etc. Furthermore, significant predominance of C > T transitions which were unique to HLNRA group was observed preferentially at CpG dinucleotide regions. Analysis with REVEL and AloFT tools did not show any increase in potentially pathogenic mutations including those involved in carcinogenesis in HLNRA individuals exposed to chronic radiation.</p><p><strong>Conclusion: </strong>This study did not show any significant changes in genetic variants due to long term exposure to LDIR in human population living in HLNRAs of Kerala coast. However, presence of unique SNVs and C > T transitions in CpG islands of HLNRA individuals indicate the possible role of epigenetic mechanisms i.e. DNA methylation in response to chronic LDIR in this population. This study significantly enhances the current understanding of radiation induced genetic changes and associated cancer risk in human population.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12958757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316856","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":"Development of a DNA damage assay system using stable human hepatocytes.","authors":"Masayuki Mishima, Kazuki Izawa, Masataka Tsuda, Yuichiro Higuchi, Shotaro Uehara, Hiroshi Suemizu, Kei-Ichi Sugiyama","doi":"10.1186/s41021-025-00347-7","DOIUrl":"10.1186/s41021-025-00347-7","url":null,"abstract":"<p><strong>Background: </strong>Overcoming species differences in metabolism between humans and animals remains a critical challenge in toxicological studies. Rat liver S9 fraction has long been the gold standard for exogenous metabolic activation in in vitro genotoxicity tests. Experiences with human S9 or human primary hepatocytes have suggested that the human materials are unsuitable for standardized testing due to high variability. Nevertheless, there is growing interest in genotoxicity evaluation using metabolic systems that more closely mimic human physiology.</p><p><strong>Results: </strong>We developed an in-cell ELISA system to measure γH2AX as a DNA damage marker in stable human hepatocytes (γH2AX-SHE). HepaSH cells are consistently available human hepatocytes that stably express a range of metabolic enzymes and drug transporters in vitro. Due to their highly differentiated and non-proliferative nature, conventional genotoxicity endpoints such as micronuclei formation, chromosomal aberrations, or mutant colony assays are not applicable. We used γH2AX, a sensitive DNA damage marker, in this assay system. Indirect mutagens including benzo(a)pyrene, aristolochic acid, and 2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine induced dose-dependent increases in γH2AX across all three HepaSH strains. Time-course analysis following benzo(a)pyrene exposure indicated that a treatment duration of 16 hours or longer was necessary to detect genotoxic responses. Prolonged exposure for 48 hours resulted in extensive cell death, which may interfere with γH2AX quantification.</p><p><strong>Conclusions: </strong>We demonstrated that γH2AX-SHE can serve as a valuable tool for detecting DNA damage under conditions that mimic human metabolic activity. Based on the findings in this study, we recommend the following assay conditions for γH2AX-SHE: a 24-hour treatment period, a DMSO concentration not exceeding 1%, and careful interpretation of positive responses observed at highly cytotoxic doses - defined as approximately less than 60% cell survival - as these may lack biological relevance.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"48 1","pages":"3"},"PeriodicalIF":2.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12849352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146062518","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":"CYP1B1- and CYP1A1-Template systems and their application to metabolism and inhibition.","authors":"Yasushi Yamazoe, Kaori Ambe, Masahiro Tohkin, Takashi Yamada, Kenichi Masumura","doi":"10.1186/s41021-025-00351-x","DOIUrl":"10.1186/s41021-025-00351-x","url":null,"abstract":"<p><p>Prediction of cytochrome P450 (CYP)-mediated metabolism is crucial for assessing the safety of chemicals. An in silico system to reproduce CYP1B1-mediated reactions has been developed by the reverse construction of ligand-accessible spaces from ligand assemblies as a fused grid Template* system. There are close similarities between Templates of CYP1B1 and previously established CYP1A1 (Genes & Environ 2023) in the distribution area, Site of oxidation, and the available Width, except for the use of Position 52’ (Pier-sitting) and the lack of use of the bottom in the middle region (Rings F and Ea) on CYP1B1-Template. Experiments using various substrates of both enzymes further suggested the distinct localization of Bay-2 residues on Templates of CYP1A1 and CYP1B1. More than 260 reactions of CYP1A1/1B1 ligands were examined on the present CYP1A1- and CYP1B1-Template systems. From their placements on the Templates and rules for interaction modes, verifications of good and poor substrates, regio/stereo-selectivity, and inhibition became faithfully available for these ligands. To understand the structural basis of the inhibitory interaction, various inhibitors were applied to the Templates and verified modes of the steric interactions. Both the hangings at Position 32 of CYP1A1 ligands and the adherence at Positions 24–52 of CYP1B1 ligands are suggested to retard the dissociation of Bay-2 residues from ligand molecules. Dissociation interference of ligands with Bay-2 residue is thus possible to be a mechanism of ligand-mediated inhibition on CYP1A1 and CYP1B1.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"1"},"PeriodicalIF":2.0,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12781794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843620","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":"Guidelines for the assessment and control of mutagenic impurities in pharmaceuticals.","authors":"Masamitsu Honma","doi":"10.1186/s41021-025-00349-5","DOIUrl":"10.1186/s41021-025-00349-5","url":null,"abstract":"<p><p>Pharmaceuticals may contain trace impurities unrelated to therapeutic activity, which may occur as synthetic intermediates or degradation products. Among these impurities, mutagenic impurities are of particular concern, as even very low levels of exposure can increase the risk of cancer in humans. To address this issue, the International Council on Harmonization (ICH) developed the M7 guideline in 2014, which aim to provide a scientific and practical framework for the assessment and control of mutagenic impurities in pharmaceuticals. The M7 guideline has been updated twice, in 2017 (R1) and 2023 (R2), with the addition of addendum defining compound-specific acceptable intake levels and a comprehensive Q&A document to promote harmonized implementation. Recent cases involving N-nitrosamine impurities have highlighted the need for improved risk assessment methods due to their high carcinogenic potential. The latest revision of the M7 guidelines (M7(R3)) will introduce a new approach to consider the quantitative carcinogenic potential of N-nitrosamines based on their structural characteristics.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"26"},"PeriodicalIF":2.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12723853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809539","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":"Genotoxicity assessment of mesoporous silica and graphene oxide in GDL1 cells.","authors":"Rikako Ishigamori, Akiko Ohno, Kiyoshi Fukuhara, Shinya Hasegawa, Yukari Totsuka","doi":"10.1186/s41021-025-00350-y","DOIUrl":"10.1186/s41021-025-00350-y","url":null,"abstract":"<p><strong>Background: </strong>Nanomaterials such as mesoporous silica and graphene oxide are increasingly used in industrial, medical, and cosmetic applications due to their unique physical and chemical properties. However, their potential genotoxicity remains poorly understood. To evaluate the associated health risks of mesoporous silica and graphene oxide, we assessed their cytotoxicity and genotoxicity in GDL1 cells using trypan blue exclusion and gpt mutation assays, followed by mutation frequency and spectrum analysis through gpt gene sequencing.</p><p><strong>Results: </strong>A 24-hour exposure of mesoporous silica to GDL1 cells induced dose-dependent reductions in cell viability, as well as dose-dependent increases in gpt mutation frequencies at 0.06 and 0.09 mg/mL. Graphene oxide induced cytotoxicity at higher concentrations (0.2 and 0.4 mg/mL) and significantly increased gpt mutation frequency in the highest concentration exposure group compared to controls. Mutation spectrum analysis revealed a significant increase in G: C to A: T transitions in both the exposed groups. In addition, exposure to mesoporous silica significantly increased G: C to T: A transversions, while graphene oxide exposure significantly increased G: C to C: G transversions. Mutation hotspots at positions 64, 164, and 416 in the gpt gene were identified exclusively in the mesoporous silica-treated group, indicating material-specific mutagenesis. Mutations at position 401 were detected exclusively in the graphene oxide group, indicating this site as a potential mutation hotspot.</p><p><strong>Conclusion: </strong>These results demonstrate that both mesoporous silica and graphene oxide exhibit cytotoxic and genotoxic potential in vitro. The mutation patterns suggest that oxidative DNA damage, as well as inflammation associated with oxidative stress, may contribute to the observed mutagenicity. The findings reported here provide valuable insights into the molecular mechanisms underlying the mutagenicity induced by these nanomaterials and contribute to the assessment of potential human health risks.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"2"},"PeriodicalIF":1.9,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12781440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145819078","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":"Antimutagenic effects of a tea made from Actinidia arguta, sarunashi in Japanese, and its inhibitory effects on the formation of aberrant crypt foci induced by 1,2-dimethylhydrazine in mice.","authors":"Yusuke Saiki, Naoko Miyake, Sakae Arimoto-Kobayashi","doi":"10.1186/s41021-025-00348-6","DOIUrl":"10.1186/s41021-025-00348-6","url":null,"abstract":"<p><p>We previously determined the antimutagenic activity of the juice of Actinidia arguta (hereafter referred to as sarunashi-juice) using the Ames test. The anticarcinogenic effect of sarunashi-juice was observed in lung and skin tumorigenesis in mice. We hypothesized that tea prepared from the leaves and twigs of A. arguta (hereafter referred to as sarunashi-tea) might also have antimutagenic and anticarcinogenic properties. We investigated the antimutagenic activity of sarunashi-tea using the Ames test, and its preventive effects on the formation of aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH) in mice. Antimutagenic results against aflatoxin B1, benzo(a)pyrene (B(a)P), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and 1-methyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2-amine (PhIP) were observed with the administration of sarunashi-tea. The amounts of sarunashi-tea needed for 50% inhibition (ID50) toward B(a)P, MeIQx, and Trp-P-2 were 2.9, 2.5, and 6.3 times higher, respectively, than that of sarunashi-juice. The antimutagenic components present in the juice and tea prepared from sarunashi may be similar chemicals. However, the concentration of the antimutagenic substances may be 2.5–6.3 times lower in sarunashi-tea than in sarunashi-juice. The total number of ACF was significantly reduced in mice treated with DMH in the presence of sarunashi-tea compared to that in mice treated with DMH in the absence of sarunashi-tea. Further investigation of the mechanisms of antimutagenicity and anti-ACF formation and identification of active components in sarunashi-tea will be worthwhile.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"25"},"PeriodicalIF":2.0,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12723940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809456","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":"Development of a novel in vitro micronucleus test using human induced pluripotent stem cell-derived T lymphocytes.","authors":"Ryota Kobayashi, Katsunori Sasaki, Ryoko Matsuyama, Koichi Saito, Ayako Kumagai, Shuichi Kitayama, Yohei Kawai, Shin Kaneko","doi":"10.1186/s41021-025-00345-9","DOIUrl":"10.1186/s41021-025-00345-9","url":null,"abstract":"<p><strong>Background: </strong>Various immortalized cells and human fresh blood lymphocytes have been used in in vitro genotoxicity studies (e.g., micronucleus (MN) test). Although immortalized cells can be supplied stably, their properties are different from normal cells such as abnormal karyotype. Human fresh blood lymphocytes are representative human normal cells, but homogenous lymphocytes are difficult to supply stably and in a timely manner due to individual differences between donors. Here, we aimed to develop a novel in vitro MN test using human induced pluripotent stem cell (hiPSC)-derived T lymphocytes to overcome the above problems.</p><p><strong>Results: </strong>hiPSCs were differentiated to T lymphocytes, which were confirmed to possess the ability to grow well in culture, a normal karyotype, and a spontaneous frequency of micronuclei. The genotoxicity of several reference positive / negative control substances was evaluated. The responses for all test substances, including clastogen, aneugen and negative substances, were consistent with published reports.</p><p><strong>Conclusions: </strong>Our results demonstrated promising proof-of-principle data as an in vitro MN test and suggest that hiPSC-derived T lymphocytes have a potential to make a significant contribution to the improvement of in vitro genotoxicity studies.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"47 1","pages":"24"},"PeriodicalIF":1.9,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12673778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The science behind safety in our daily life: the open symposium of the Japanese environmental mutagen and genome society (JEMS), 2025.","authors":"Naoki Koyama, Masataka Tsuda","doi":"10.1186/s41021-025-00346-8","DOIUrl":"10.1186/s41021-025-00346-8","url":null,"abstract":"<p><p>The open symposium of the Japanese Environmental Mutagen and Genome Society (JEMS) entitled \"The Science Behind Safety in Our Daily Lives,\" was held as a hybrid in-person and online meeting on June 14, 2025. The rapid advancement of science and technology continues to profoundly alter our lifestyles. We face potential risks from chemical, biological, and physical agents, including chemical substances, bacteria/viruses, and radioactive substances, particularly in pharmaceuticals, food, and indoor environments. Furthermore, natural disasters such as earthquakes and heavy rains not only cause physical damage, but can also lead to health hazards from chemical substances and radiation. This underscores the urgent need for robust systems that can effectively respond to health crises. This symposium aimed to improve public understanding of safety science in daily life, including in pharmaceuticals, food, and living environments. In this symposium, we invited five scientists who are expanding the frontiers of health sciences. We organized this public event to be open to everyone, not just members of the JEMS. Herein, the organizers present a summary of the symposium.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"47 1","pages":"23"},"PeriodicalIF":1.9,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12625554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145549227","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}