Pharmacological Reports最新文献

{"title":"The future of metronomic chemotherapy: experimental and computational approaches of drug repurposing.","authors":"Yousef A Abdelrady, Hayam S Thabet, Ahmed M Sayed","doi":"10.1007/s43440-024-00662-w","DOIUrl":"10.1007/s43440-024-00662-w","url":null,"abstract":"<p><p>Metronomic chemotherapy (MC), long-term continuous administration of anticancer drugs, is gaining attention as an alternative to the traditional maximum tolerated dose (MTD) chemotherapy. By combining MC with other treatments, the therapeutic efficacy is enhanced while minimizing toxicity. MC employs multiple mechanisms, making it a versatile approach against various cancers. However, drug resistance limits the long-term effectiveness of MC, necessitating ongoing development of anticancer drugs. Traditional drug discovery is lengthy and costly due to processes like target protein identification, virtual screening, lead optimization, and safety and efficacy evaluations. Drug repurposing (DR), which screens FDA-approved drugs for new uses, is emerging as a cost-effective alternative. Both experimental and computational methods, such as protein binding assays, in vitro cytotoxicity tests, structure-based screening, and several types of association analyses (Similarity-Based, Network-Based, and Target Gene), along with retrospective clinical analyses, are employed for virtual screening. This review covers the mechanisms of MC, its application in various cancers, DR strategies, examples of repurposed drugs, and the associated challenges and future directions.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1-20"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ONC206, an imipridone derivative, demonstrates anti-colorectal cancer activity against stem/progenitor cells in 3D cell cultures and in patient-derived organoids.","authors":"Alissar Monzer, Fatima Ghamlouche, Kevork Wakimian, Farah Ballout, Samar Al Bitar, Amani Yehya, Mariam Kanso, Nour Saheb, Ayman Tawil, Samer Doughan, Maher Hussein, Deborah Mukherji, Walid Faraj, Joshua E Allen, Varun V Prabhu, Tamara Abou-Antoun, Hala Gali-Muhtasib, Wassim Abou-Kheir","doi":"10.1007/s43440-024-00676-4","DOIUrl":"10.1007/s43440-024-00676-4","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) remains one of the most frequently diagnosed and life-threatening malignancies worldwide. CRC's high recurrence rates and drug resistance have been correlated with a subpopulation of dormant slowly dividing cells termed CRC stem cells (CCSCs). Consequently, there is a pressing need to identify novel therapeutics that can effectively and specifically target CCSCs. Imipridones are promising structurally related anticancer molecules that showed efficacy in several solid and hematological preclinical models and phase I/II/III clinical trials. This study mainly aimed to assess the potential anticancer effects of ONC206, an imipridone derivative, on CRC three-dimensional in vitro culture systems using HCT116 and HT29 cells. Importantly, the study aimed at using CRC patient-derived organoids (PDOs) to test the potential therapeutic effect of ONC206.</p><p><strong>Methods: </strong>Two-dimensional cell proliferation, viability, migration, and invasion assays were used to assess the effects of ONC206 on two colorectal cancer cell lines, HCT116 and HT29, in vitro. Immunofluorescence imaging, flow cytometry, and western blot analysis were also performed to investigate the mechanism of action of this drug. Sphere formation assay and CRC PDOs were employed to evaluate the effect of ONC206 on CRC cells in a 3D setting and specifically its potency in targeting the CRC stem/progenitor subpopulation of cells.</p><p><strong>Results: </strong>Our results showed that ONC206 was more potent than its parental molecule ONC201 in inhibiting the proliferation and viability of HCT116 and HT29 cells. Moreover, ONC206 significantly reduced the migration and invasion indices of CRC cells. These effects were accompanied by an increase in reactive oxygen species (ROS) production, sub-G1 phase accumulation, and apoptosis in HCT116 and HT29 cells. Furthermore, ONC206 significantly inhibited the 3D colonospheres growth and self-renewal ability of CCSCs more potently than ONC201, which was associated with a decrease in the expression of CSC-related markers. Lastly, ONC206 significantly reduced the growth of organoids derived from CRC patients.</p><p><strong>Conclusion: </strong>Collectively, our findings demonstrate that ONC206 is an effective anticancer molecule capable of targeting CCSCs, which may represent a novel therapeutic strategy that can overcome CRC resistance and recurrence.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"229-246"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of puerarin on gait disturbance in a 6-hydroxydopamine mouse model of Parkinson's disease.","authors":"Na-Hyun Kim, Yukiori Goto, Young-A Lee","doi":"10.1007/s43440-024-00673-7","DOIUrl":"10.1007/s43440-024-00673-7","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is a neurodegenerative disorder caused by dopamine (DA) neuronal dysfunction. Although DA agonists and N-methyl-D-aspartate receptor (NMDAR) antagonists are used to treat PD, chronic use causes severe side effects. Puerarin (PUE) is a natural bioactive compound that affects the DA system; however, its effect on PD-associated motor functions is unknown. Therefore, we investigated whether PUE treatment in a 6-hydroxydopamine (6-OHDA) PD mouse model affects motor dysfunction.</p><p><strong>Methods: </strong>Adult male ICR mice received unilateral 6-OHDA microinfusion into the right medial forebrain bundle. After a 2-week recovery period, PUE (20 or 50 mg/kg) or the vehicle (saline, VEH) was administered intraperitoneally once daily for 21 days. Motor dysfunction was assessed using the locomotion, gait cycle, and rotation tests. Local field potentials (LFPs) were measured in the substantia nigra compacta (SNc), striatum (STR), subthalamic nucleus (STN), and primary motor cortex.</p><p><strong>Results: </strong>6-OHDA-lesioned PD mice showed increased gait cycle disturbance and unidirectional rotation. PUE treatment ameliorated the gait cycle disturbance, but not unidirectional rotation of PD mice. These effects differed with DA agonist treatment (which improved PD symptoms) and NMDAR antagonist treatment (which aggravated PD symptoms). Moreover, locomotion was increased only in NMDAR antagonist treatment. PUE treatment induced no changes in the attenuated LFP of the beta wave in the STR and STN, and SNc-STN delta-wave coherence was shown in PD animals.</p><p><strong>Conclusions: </strong>This study suggests that PUE is a beneficial co-therapeutic agent for alleviating gait cycle disturbance in PD symptoms.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"247-259"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive update on the potential of curcumin to enhance chemosensitivity in colorectal cancer.","authors":"Mahdi Shadnoush, Mehrnaz Momenan, Veronique Seidel, Sascha Tierling, Nayeralsadat Fatemi, Ehsan Nazemalhosseini-Mojarad, Mohammad Tayefeh Norooz, Makan Cheraghpour","doi":"10.1007/s43440-024-00652-y","DOIUrl":"10.1007/s43440-024-00652-y","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the most common cancers and a major cause of cancer-related mortality worldwide. The efficacy of chemotherapy agents in CRC treatment is often limited due to toxic side effects, heterogeneity of cancer cells, and the possibility of chemoresistance which promotes cancer cell survival through several mechanisms. Combining chemotherapy agents with natural compounds like curcumin, a polyphenol compound from the Curcuma longa plant, has been reported to overcome chemoresistance and increase the sensitivity of cancer cells to chemotherapeutics. Curcumin, alone or in combination with chemotherapy agents, has been demonstrated to prevent chemoresistance by modulating various signaling pathways, reducing the expression of drug resistance-related genes. The purpose of this article is to provide a comprehensive update on studies that have investigated the ability of curcumin to enhance the efficacy of chemotherapy agents used in CRC. It is hoped that it can serve as a template for future research on the efficacy of curcumin, or other natural compounds, combined with chemotherapy agents to maximize the effectiveness of therapy and reduce the side effects that occur in CRC or other cancers.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"103-123"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the effects of 5-HT_2A and 5-HT_5A receptor antagonists on DOI-induced head-twitch response in male rats using marker-less deep learning algorithms.","authors":"Ewelina Cyrano, Piotr Popik","doi":"10.1007/s43440-024-00679-1","DOIUrl":"10.1007/s43440-024-00679-1","url":null,"abstract":"<p><strong>Background: </strong>Serotonergic psychedelics, which display a high affinity and specificity for 5-HT_2A receptors like 2,5-dimethoxy-4-iodoamphetamine (DOI), reliably induce a head-twitch response in rodents characterized by paroxysmal, high-frequency head rotations. Traditionally, this behavior is manually counted by a trained observer. Although automation could simplify and facilitate data collection, current techniques require the surgical implantation of magnetic markers into the rodent's skull or ear.</p><p><strong>Methods: </strong>This study aimed to assess the feasibility of a marker-less workflow for detecting head-twitch responses using deep learning algorithms. High-speed videos were analyzed using the DeepLabCut neural network to track head movements, and the Simple Behavioral Analysis (SimBA) toolkit was employed to build models identifying specific head-twitch responses.</p><p><strong>Results: </strong>In studying DOI (0.3125-2.5 mg/kg) effects, the deep learning algorithm workflow demonstrated a significant correlation with human observations. As expected, the preferential 5-HT_2A receptor antagonist ketanserin (0.625 mg/kg) attenuated DOI (1.25 mg/kg)-induced head-twitch responses. In contrast, the 5-HT_5A receptor antagonists SB 699,551 (3 and 10 mg/kg), and ASP 5736 (0.01 and 0.03 mg/kg) failed to do so.</p><p><strong>Conclusions: </strong>Previous drug discrimination studies demonstrated that the 5-HT_5A receptor antagonists attenuated the interoceptive cue of a potent hallucinogen LSD, suggesting their anti-hallucinatory effects. Nonetheless, the present results were not surprising and support the head-twitch response as selective for 5-HT_2A and not 5-HT_5A receptor activation. We conclude that the DeepLabCut and SimBA toolkits offer a high level of objectivity and can accurately and efficiently identify compounds that induce or inhibit head-twitch responses, making them valuable tools for high-throughput research.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"135-144"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Select terpenes from Cannabis sativa are antinociceptive in mouse models of post-operative pain and fibromyalgia via adenosine A_2a receptors.","authors":"Caleb A Seekins, Alyssa M Welborn, Abigail M Schwarz, John M Streicher","doi":"10.1007/s43440-024-00687-1","DOIUrl":"10.1007/s43440-024-00687-1","url":null,"abstract":"<p><strong>Background: </strong>Terpenes from Cannabis show promise for pain management. Our lab found that the terpenes geraniol, linalool, β-caryophyllene, and α-humulene relieve chemotherapy-induced peripheral neuropathy via Adenosine A_2a receptors (A_2aR). This suggests terpenes as potential non-opioid, non-cannabinoid therapeutics. In this study, we investigated post-operative and fibromyalgia pain, expanding potential terpene applications to different pain types.</p><p><strong>Methods: </strong>Male and female CD-1 mice had their baseline mechanical sensitivity measured via von Frey filaments and underwent either paw incision surgery or reserpine-induced fibromyalgia (0.32 mg/kg, sc). After pain was established, the mice received 200 mg/kg ip of a terpene, and their mechanical sensitivity was measured over three hours. To determine the potential mechanism of action, mice were given the A_2aR antagonist istradefylline (3.2 mg/kg, ip) 10 min before terpene, with mechanical sensitivity measured after. Hot plate pain testing was performed as a control.</p><p><strong>Results: </strong>Terpene treatment caused time-dependent elevation of the mechanical thresholds of the mice from both pain models, strongest for geraniol, then linalool or α-humulene, indicating that these four terpenes are anti-nociceptive in post-surgical and fibromyalgia pain. Pretreatment with istradefylline blocked antinociception, suggesting the terpenes act via the A_2aR in these pain models. Terpenes had no effect on hot plate latencies, ruling out non-specific motor effects.</p><p><strong>Conclusions: </strong>These results demonstrate that the terpenes geraniol, linalool, β-caryophyllene, and α-humulene may be a viable medication for post-operative and fibromyalgia pain relief. Their mechanism of action via the A_2aR furthers our knowledge of its importance in pain processing and as a target of terpene drugs.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"172-181"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ursolic acid in colorectal cancer: mechanisms, current status, challenges, and future research directions.","authors":"Huici Zhang, Xiaoyu Zhang, Xijun Ma, Xuan Wang","doi":"10.1007/s43440-024-00684-4","DOIUrl":"10.1007/s43440-024-00684-4","url":null,"abstract":"<p><p>Colorectal cancer (CRC) ranks as the third most prevalent cancer globally, contributing to approximately 10% of all cancer cases and representing the second leading cause of cancer-related mortality worldwide. Ursolic acid (UA), a widely studied pentacyclic triterpenoid, has attracted substantial attention from researchers and clinicians due to its potential therapeutic effects against malignant tumors. Multiple studies have confirmed that UA inhibits tumor cell proliferation, induces differentiation and apoptosis, suppresses invasion, and impedes tumor angiogenesis via diverse mechanisms. However, research specifically addressing UA's anti-CRC effects remains limited, and systematic reviews of its underlying mechanisms in CRC are scarce. This study seeks to provide a comprehensive review of UA's mechanisms of action against CRC, offering valuable insights and references for researchers and clinicians.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"72-86"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long noncoding RNA MEG3: an active player in fibrosis.","authors":"Xiaoying Jiang","doi":"10.1007/s43440-024-00661-x","DOIUrl":"10.1007/s43440-024-00661-x","url":null,"abstract":"<p><p>Fibrosis, characterized by excess accumulation of extracellular matrix components, disrupts normal tissue structure and causes organ dysfunction. Long noncoding RNAs (lncRNAs) are a subset of RNAs longer than 200 nucleotides that are not converted into proteins. The increasing research indicated that lncRNA maternally expressed gene 3 (MEG3) was dysregulated in the pathologic process of fibrosis in several tissues. LncRNA MEG3 was revealed to regulate the expression of target proteins or serve as a miRNAs sponge to control the development of fibrosis, which was involved in NF-ҡB, PI3K/AKT, JAK2/STAT3, Wnt/β-catenin, ERK/p38, and Hh pathway. Importantly, the interference of MEG3 level ameliorated fibrosis. The present review summarized available studies of lncRNA MEG3 in fibrosis, which is helpful for a deeper understanding of the roles of MEG3 in fibrosis.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"21-30"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acyclic sesquiterpenes nerolidol and farnesol: mechanistic insights into their neuroprotective potential.","authors":"Anish Singh, Lovedeep Singh","doi":"10.1007/s43440-024-00672-8","DOIUrl":"10.1007/s43440-024-00672-8","url":null,"abstract":"<p><p>Sesquiterpenes are a class of organic compounds found in plants, fungi, and some insects. They are characterized by the presence of three isoprene units, resulting in a molecular formula that typically contains 15 carbon atoms (C₁₅H₂₄). Nerolidol and farnesol are both sesquiterpene alcohols present in the essential oils of numerous plants. They have drawn attention due to their potential neuroprotective properties. Nerolidol and farnesol are structural isomers, specifically geometric isomers, haring the same molecular formula (C₁₅H₂₄O) but differing in the spatial arrangement of their atoms. This variation in structure may contribute to their distinct biological activities. Scientific evidence suggests that nerolidol and farnesol exhibit antioxidant and anti-inflammatory characteristics which are crucial for neuroprotection. Nerolidol has been specifically noted for its ability to alleviate conditions such as Alzheimer's disease, Parkinson's disease, encephalomyelitis, depression, and anxiety by modulating inflammatory and oxidative stress pathways. Moreover, research indicates that both nerolidol and farnesol may modulate the Nrf-2/HO-1 antioxidant signaling pathway to mitigate oxidative stress-induced neurological damage. Activation of Nrf-2/HO-1 signaling cascade promotes cell survival and enhances the brain's ability to resist various insults. Nerolidol has also been reported to alleviate neuroinflammation by inhibiting the TLR-4/NF-κB and COX-2/NF-κB inflammatory signaling pathway. Besides, this nerolidol also modulates BDNF/TrkB/CREB signaling pathway to improve neuronal health. To date, limited research has delved into the anti-inflammatory properties of farnesol concerning neurodegenerative diseases. Further investigation is warranted to comprehensively elucidate the mechanisms underlying its action and potential therapeutic uses in neuroprotection. Initial observations indicate that farnesol exhibits promising prospects as a natural agent for safeguarding brain functions. Henceforth, drawing upon existing literature elucidating the neuroprotective attributes of nerolidol and farnesol, the current review endeavors to provide a detailed analysis of their mechanistic underpinnings in neuroprotection.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"31-42"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer potential of osthole: targeting gynecological tumors and breast cancer.","authors":"Yingqi Han, Zhengao Sun","doi":"10.1007/s43440-024-00685-3","DOIUrl":"10.1007/s43440-024-00685-3","url":null,"abstract":"<p><p>Gynecological tumors, such as ovarian, endometrial, and cervical cancers, alongside breast cancer, represent significant malignancies that pose serious threats to women's health worldwide. Standard treatments, including surgery, chemotherapy, radiotherapy, and targeted therapies, are commonly utilized in clinical practice. However, challenges such as high recurrence rates, drug resistance, and adverse side effects underscore the urgent need for more effective therapeutic options. Osthole, a natural coumarin compound derived from Chinese herbal medicine, has demonstrated remarkable antitumor activity against various cancers. Emerging evidence indicates that osthole can inhibit the proliferation, invasion, and metastasis of gynecological and breast cancer cells through various mechanisms, including inducing apoptosis and autophagy, regulating the tumor microenvironment, inhibiting tumor angiogenesis, and enhancing the sensitivity of cancer cells to chemotherapy and radiotherapy. This review highlights the recent advancements in osthole research within the context of gynecological and breast cancers, focusing on its molecular mechanisms, and offers a theoretical foundation for its potential development as an anticancer agent.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"87-102"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}