Phytotherapy Research最新文献

{"title":"Triptolide Promotes Ferroptosis in Cervical Cancer Cell via NRF2/xCT/GPX4.","authors":"Miaomiao Feng, Haiwang Wu, Ling Zhu, Jie Gao, Gaopi Deng","doi":"10.1002/ptr.8398","DOIUrl":"10.1002/ptr.8398","url":null,"abstract":"<p><p>Cervical cancer (CC) is a serious risk to women's health; it is necessary to explore less toxic and more effective therapies to cure CC. Triptolide (Tri) is the principal active constituent found in \"Tripterygium Wilford,\" has been shown to have antitumor effects. This study set up to demonstrate whether Tri is capable of inducing ferroptosis in CC cells and its potential mechanism. In vitro, Tri was used to treat CC cells, and lipid peroxidation levels in CC cells were detected by flow cytometry, immunofluorescence, and other experiments; the molecular mechanism of Tri treatment of CC was explored by western blot; moreover, the regulatory effects of Tri on the NRF2/GPX4/xCT axis were verified by overexpressing NRF2 in reverse. In vivo, CC cells tumor-bearing mice were constructed to observe the effect of Tri treatment on tumor growth. In vitro, we have demonstrated that Tri prevents the growth and migration of CC cells. Further investigation revealed that Tri substantially enhances ferroptosis in CC cells by increasing lipid peroxidation accumulation. Mechanically, Tri significantly reduced the expression of NRF2, leading to a corresponding repression of the NRF2 downstream targets GPX4 and xCT. Moreover, overexpressing of NRF2 effectively reversed the impact of Tri on ferroptosis in CC cells. Additionally, animal experiments indicted that Tri markedly inhibited tumor size in nude mice by inhibiting the NRF2/GPX4/xCT axis. Tri exerts antitumor effects by triggering ferroptosis in CC cells through the NRF2/GPX4/xCT axis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"875-887"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suffruticosol B from Paeonia lactiflora Ameliorates Alzheimer's Disease Pathology by Inhibiting MAO-B Activity.","authors":"Jae-Jun Heo, Young-Eun Han, Min Soo Kim, Eunji Cheong, Chun Whan Choi, Soo-Jin Oh","doi":"10.1002/ptr.8395","DOIUrl":"10.1002/ptr.8395","url":null,"abstract":"<p><p>Monoamine oxidase B (MAO-B) has emerged as a therapeutic target for Alzheimer's disease (AD) due to its involvement in the synthesis of γ-aminobutyric acid (GABA) in reactive astrocytes, which inhibits neuronal activity. Suffruticosol B (Suf-B), isolated from Paeonia lactiflora, is one of the resveratrol oligomers. Although resveratrol oligomers have demonstrated neuroprotective effects, it remains unexplored whether Suf-B exerts therapeutic effects on AD by targeting MAO-B. In this study, we investigated whether Suf-B alleviates AD pathology by mitigating reactive astrogliosis and inhibiting the overproduction of astrocytic GABA. After confirming the MAO-B inhibitory effect of Suf-B through MAO-B enzyme assay, we administered Suf-B to APP/PS1 AD model mice. To test the potential therapeutic action of Suf-B in AD, a series of experiments were conducted, including behavioral tests such as the open field test, novel object recognition test, Barnes maze test, passive avoidance test, as well as immunohistochemistry and whole-cell patch-clamp recordings. We found that Suf-B markedly inhibited MAO-B activity without causing cytotoxicity. Immunohistochemistry and electrophysiology experiments demonstrated that Suf-B significantly reduced astrocyte reactivity, as well as an aberrant increase in GABA production and tonic GABA release from astrocytes in AD. Behavior test results indicated that Suf-B treatment restored cognitive function in APP/PS1 mice. In conclusion, Suf-B effectively reduces excessive GABA production in reactive astrocytes by inhibiting MAO-B, normalizing aberrant inhibition in hippocampal neurons in an AD mouse model. These results suggest that Suf-B has potential as a treatment for AD and may be applicable to other brain diseases associated with reactive astrogliosis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"593-603"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking Natural Potential: Antibody-Drug Conjugates With Naturally Derived Payloads for Cancer Therapy.","authors":"Xue Jiang, Wan Najbah Nik Nabil, Yufei Ze, Rongchen Dai, Zhichao Xi, Hongxi Xu","doi":"10.1002/ptr.8407","DOIUrl":"10.1002/ptr.8407","url":null,"abstract":"<p><p>Natural compound-derived chemotherapies remain central to cancer treatment, however, they often cause off-target side effects that negatively impact patients' quality of life. In contrast, antibody-drug conjugates (ADCs) combine cytotoxic payloads with antibodies to specifically target cancer cells. Most approved and clinically investigated ADCs utilize naturally derived payloads, while those with conventional synthetic molecular payloads remain limited. This review focuses on approved ADCs that enhance the efficacy of naturally derived payloads by linking them with antibodies. We provide an overview of the core components of ADCs, their working mechanisms, and FDA-approved ADCs featuring naturally derived payloads, such as calicheamicin, camptothecin, dolastatin 10, maytansine, pyrrolbenzodiazepine (PBD), and the immunotoxin Pseudomonas exotoxin A. This review also explores recent clinical advancements aimed at broadening the therapeutic potential of ADCs, their applicability in treating heterogeneously composed tumors and their potential use beyond oncology. Additionally, this review highlights naturally derived payloads that are currently being clinically investigated but have not yet received approval. By summarizing the current landscape, this review provides insights into promising avenues for exploration and contributes to the refinement of treatment protocols for improved patient outcomes.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"789-874"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ilexgenin A Alleviates Myocardial Ferroptosis in Response to Ischemia Reperfusion Injury via the SIRT1 Pathway.","authors":"Bo Yang, Xiao-Yu Jue, Shang-Fei Luo, Zhang-Bin Tan, Li-Ning Yang, Yun-Ting Feng, Yong-Zhen Tan, Bin Liu, Jing-Zhi Zhang, Bo Deng, Wei-Wei Wu, Shuang-Wei Zhang","doi":"10.1002/ptr.8414","DOIUrl":"10.1002/ptr.8414","url":null,"abstract":"<p><p>Myocardial ischemia-reperfusion (I/R) injury has emerged as an increasingly serious cardiovascular health concern worldwide, with ferroptosis playing a pivotal role as the underlying pathogenic process. This study aimed to investigate the pharmacological effect and mechanism of Ilexgenin A on cardiomyocyte ferroptosis induced by myocardial I/R injury. In vivo, we established a murine anterior descending artery ligation/recanalization model to evaluate the cardioprotective effect of Ilexgenin A. Bioinformatics analysis, molecular docking, and Surface Plasmon Resonance imaging were conducted to predict the pharmacological targets of Ilexgenin A. In vitro experiments, the neonatal rat cardiomyocytes (NRCMs) were utilized to further explore the mechanism of Ilexgenin A in inhibiting ferroptosis using chemiluminescence and immunofluorescence staining, electron microscopy, biochemical assay, RT-qPCR, western blotting, and so on. The results showed that Ilexgenin A protected against cardiac dysfunction, ameliorated myocardial ferroptosis and mitochondrial damage induced by murine myocardial I/R injury via the silence information regulator 1 (SIRT1) pathway, the trend was consistently observed in NRCMs. Additionally, the SIRT1 knockdown by siRNA delivery partially abrogated the beneficial effects of Ilexgenin A on ameliorating mitochondrial damage, and then aggravated erastin-induced ferroptosis in NRCMs. Overall, Our research demonstrated that the inhibition of ferroptosis via the SIRT1 pathway was one of the mechanisms by which Ilexgenin A exerted cardioprotective effect.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"938-956"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoliquiritigenin Exhibits Anti-Inflammatory Responses in Acute Lung Injury by Covalently Binding to the Myeloid Differentiation Protein-2 Domain.","authors":"Liu Yang, Haoran Nie, Yan Du, Xuyang Liu, Bangrong Cai, Jiansheng Li","doi":"10.1002/ptr.8411","DOIUrl":"10.1002/ptr.8411","url":null,"abstract":"<p><p>Acute lung injury (ALI), a systemic inflammatory response with high morbidity, lacks effective pharmacological therapies. Myeloid differentiation protein-2 (MD2) has emerged as a promising therapeutic target for ALI. Herein, we aimed to evaluate the ability of isoliquiritigenin (ISL), a natural flavonoid found in licorice as a novel MD2 inhibitor, to inhibit lipopolysaccharide (LPS)-induced ALI. We established a mouse ALI model and a RAW 264.7 cell injury model through LPS administration. Then, lung injury was assessed through histopathological examination, and the effects of ISL were evaluated using immunofluorescence, western blotting, reverse transcription-quantitative polymerase chain reaction, flow cytometry, and enzyme-linked immunosorbent assays. In addition, the interaction between ISL and MD2 was investigated through co-immunoprecipitation and LPS displacement assays. Molecular docking and liquid chromatography/mass spectrometry analyses were employed to predict the ISL-binding domain of MD2. We found that ISL covalently bound to the Cysteine 133 residue of MD2, disrupting the formation of the LPS/MD2/toll-like receptor 4 complex, and ISL significantly suppressed proinflammatory cytokine production and reactive oxygen species generation in LPS-induced RAW264.7 cells. Moreover, ISL significantly alleviated lung injury in LPS-induced mice, reducing pulmonary microvascular permeability, inflammatory cell infiltration, and inflammatory cytokine expression. The underlying mechanism of ISL involved the inhibition of nuclear factor kappa B and the p38 mitogen-activated protein kinase pathway. Our findings supported that MD2 is the direct target of ISL in mediating its anti-inflammatory response in vivo and in vitro, and it holds potential as a therapeutic candidate for treating ALI and other inflammatory diseases.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"922-937"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol: A Narrative Review Regarding Its Mechanisms in Mitigating Obesity-Associated Metabolic Disorders.","authors":"Yichen Cai, Qiu Chen","doi":"10.1002/ptr.8416","DOIUrl":"10.1002/ptr.8416","url":null,"abstract":"<p><p>Resveratrol (RSV) is a naturally occurring astragalus-like polyphenolic compound with remarkable weight loss properties. However, the mechanism of RSV in treating obesity is unclear. In this narrative review, we explored electronic databases (PubMed) for research articles from 2021 to the present using the keywords \"resveratrol\" and \"obesity\". This article explores the mechanisms involved in the alleviation of obesity-related metabolic disorders by RSV. RSV affects obesity by modulating mitochondrial function, insulin signaling, and gut microbiota, regulating lipid metabolism, inhibiting oxidative stress, and regulating epigenetic regulation. Administering RSV to pregnant animals exhibits maternal and first-generation offspring benefits, and RSV administration to lactating animals has long-term benefits, which involve the epigenetic modulations by RSV. A comprehensive understanding of the epigenetic mechanisms of RSV regulation could help in developing drugs suitable for pregnancy preparation groups, pregnant women, and nursing infants.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"999-1019"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aloe arborescens Standardized Glycosidic Fraction Suppresses Hepatocarcinoma by Modulating TIMP1, MMP9 Genes Expression, and Inflammation/Ki67/TGFβ1 Pathway.","authors":"Zaki H Hakami, Walied Abdo, Jilan A Nazeam, Samir M Osman, Wael Goda, Sabreen E Fadl, Ahmad Alsulimani, Tohada M Al-Noshokaty, Mohie Haridy, Sulaiman Mohammed Alnasser, Ahmed Abdeen","doi":"10.1002/ptr.8412","DOIUrl":"10.1002/ptr.8412","url":null,"abstract":"<p><p>(1) Background and aim: Aloe arborescens Mill. ( A. arborescens ) is one of the most widely distributed species in the genus Aloe and has garnered widespread recognition for its anticancer properties. However, the molecular mechanisms underlying these activities have not yet been fully elucidated. This study aimed to explore the effects of the plant polar glycosidic fraction (AAG) on hepatocellular carcinoma (HCC) in an in vivo model induced by diethylnitrosamine (DEN). (2) Experimental procedure: The fraction was standardized using HPLC-PDA-MS/MS fingerprinting, and two distinct intragastric AAG dose regimens were examined (10 and 20 mg/kg) in combination with DEN 200 mg/kg. Serum alpha-fetoprotein (AFP), gamma-glutamyl transferase (γ-GGT), glutathione S-transferase placental (GST-P), mRNA expression of metabolic cytochrome enzymes (CYP1A3 and CYP2B2), inflammatory genes (nuclear factor kappa-B p65 subunit; NF-κB p65), metalloproteases 9 (MMP9), tissue inhibitors of metalloproteases (TIMP1), transforming growth factor beta 1 (TGFβ1), and histological features were assessed. (3) Key results and conclusions and implications: AAG was characterized by five major secondary metabolites: saponins, chromones, anthraquinone, and triterpenes. The fraction reduced hepatic malignancy characteristics by diminishing the size and number of altered foci and lowering hepatic cancer biomarkers, such as γ-GGT, AFP, and GST-positive foci. It also reduced the mRNA levels of CYP1A3 and CYP2B2, NF-κB p65, and MMP9, hepatic Ki-67, and TGFβ1 while upregulating TIMP1 levels. This study revealed that AAG exhibited a marked suppressive effect on HCC cell proliferation, displaying a range of mechanistic actions, including decreasing the metabolic activation of cytochrome enzymes, which consequently reduced the production of reactive oxygen species and other genes implicated in cancer development. AAG could be a significant therapeutic candidate for patients diagnosed with hepatocarcinoma.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1090-1106"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Beneficial Effects of Combined Exercise and Polyphenols in Alzheimer's Disease.","authors":"Qinghua Tan","doi":"10.1002/ptr.8422","DOIUrl":"10.1002/ptr.8422","url":null,"abstract":"<p><p>Regular exercise enhances life quality, lowers the risk of cognitive damage, and slows the advancement of Alzheimer's disease (AD). Natural compounds rich in polyphenols have garnered attention as a non-pharmacological means of treating and preventing AD. The primary component of wine, grape seeds, and nuts is polyphenols. Research suggests that polyphenols slow down the rate of neurodegeneration in AD and lessen learning impairment. Furthermore, polyphenols lessen brain impairments related to cognition. Additionally, polyphenols can specifically restructure amyloid-β (Aβ) structures and soluble oligomers into non-toxic alternative species. They have also been revealed to increase brain-derived neurotrophic factors expression, suggesting that they have a positive impact on the creation of neurotrophins. The benefits of polyphenol supplementation and exercise, which can both provide neuroprotection, have not been well studied in AD patients. This review aimed to investigate the effects of combined exercise polyphenols on inflammation, neuroprotection, several conformational toxic species of Aβ, and Aβ-induced apoptosis in AD.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1020-1034"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Products From Plants Targeting Leptin Resistance for the Future Development of Anti-Obesity Agents.","authors":"Yu Liu, Fengying Gong","doi":"10.1002/ptr.8415","DOIUrl":"10.1002/ptr.8415","url":null,"abstract":"<p><p>Obesity is a serious health threat, which has affected 16% of adults globally in 2022 and shows a trend toward youthfulness. Leptin, as a regulator of body weight, can suppress appetite and promote energy expenditure, making it potential in obesity treatment. Nevertheless, with the progress of relevant research, it is worth noting that monotherapy with leptin is not an effective strategy since most obese individuals are hyperleptinemic and resistant to leptin, where high levels of leptin fail to exert its weight-loss effects. Therefore, the potential to unlock the weight-loss properties of leptin using pharmacology to improve resistance has provided a new direction for this field. However, most synthetic medicines have retreated from the market due to their undesirable side effects, while natural products are increasingly sought after for drug development due to their minimal side effects. Indeed, natural products are ideal alternatives to oral synthetic agents since a growing body of research has demonstrated their desirable effects on improving leptin resistance through potential therapeutic targets like the JAK2/STAT3 signaling pathway, protein tyrosine phosphatase 1B, the exchange proteins directly activated by cAMP/Ras-related protein 1 signaling pathway, endoplasmic reticulum stress, pro-opiomelanocortin gene, and leptin levels. This review outlines natural products that can improve leptin resistance by inhibiting or activating these targets and evaluates their efficacy in experiments and human clinical trials, offering insights for the development of anti-obesity agents. However, more high-quality clinical research is necessary to validate these findings, as current clinical evidence is constrained by heterogeneity and small sample sizes.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1174-1189"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Complex Mechanisms of Isoflavones: From Cell Bioavailability, to Cell Dynamics and Breast Cancer.","authors":"François Ferriere, Nagham Aasi, Gilles Flouriot, Farzad Pakdel","doi":"10.1002/ptr.8417","DOIUrl":"10.1002/ptr.8417","url":null,"abstract":"<p><p>In Western countries, the increase in the consumption of soy-derived products raises the population's exposure to isoflavones. These molecules, present in many foods, have numerous effects on the body's cells, including regulation of the transcription and epigenetics, cell signaling, cell cycle, cell growth, apoptosis, and oxidative stress. However, despite the multitude of studies conducted, on these compounds, it remains difficult to draw definitive conclusions regarding their safety or dangerousness in the diet. Indeed, some epidemiological studies highlight health benefits in consuming isoflavone-rich foods, notably by reducing the risk of certain cancers. However, several studies conducted on cell models show that these molecules can have negative effects on cell fate, particularly with regard to proliferation and survival of mammary tumor cells. Isoflavones are mainly genistein, daidzein, formononetin, and biochanin A. These molecules belong to the family of phytoestrogens, which are capable of interacting with both nuclear estrogen receptor, ERα and ERβ, to trigger agonistic and antagonistic effects. Due to their estrogenic properties, isoflavones are suspected to promote hormone-dependent cancers such as breast cancer. This suspicion is based primarily on their ability to bind to ERα in breast cells, thereby altering the signaling pathways that control cell growth. However, study results are sometimes contradictory. Some studies suggest that isoflavones may protect against breast cancer by acting as selective estrogen receptor modulators, while others highlight their potential role in stimulating tumor growth. This review explores the literature on the effects of isoflavones, focusing on their influence on ERα-dependent signaling in breast tumor cells.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"957-979"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}