Bingqing Cui, Jianming Wei, Huiting Peng, Ting Xu, Mengfei Chen, Yuchen Zhao, Hanshuang Cai, Bo Liu, Jing Shi
{"title":"SphK Inhibitor ZFP-B34 Suppresses the Growth of TNBC Cells.","authors":"Bingqing Cui, Jianming Wei, Huiting Peng, Ting Xu, Mengfei Chen, Yuchen Zhao, Hanshuang Cai, Bo Liu, Jing Shi","doi":"10.1248/bpb.b24-00854","DOIUrl":"https://doi.org/10.1248/bpb.b24-00854","url":null,"abstract":"<p><p>Sphingosine kinase 1/2 (SphK1/2) promote the initiation and advancement of breast cancers. We performed screening on a compound library of SphK inhibitors using computer molecular docking and selected the most representative compound, ZFP-B34, for testing its antitumor activity in triple-negative breast cancer (TNBC). In TNBC cell lines ZFP-B34 effectively inhibits SphK1/2 activity, induces ceramide accumulation, and results in Sphingosine 1 phosphate (S1P) depletion without altering SphK1/2 expression in TNBC cells, making it a promising novel dual inhibitor of SphK1/2. ZFP-B34 effectively inhibits cell proliferation, cell cycle progression, and migration, leading to cellular growth arrest. ZFP-B34 induces reactive oxygen species (ROS) production and mitochondrial depolarization, leading to mitochondrial dysfunction. Simultaneously, it damages DNA, ultimately resulting in apoptosis. ZFP-B34 can also inhibit the activation of Akt-mammalian target of rapamycin (mTOR) while inducing c-Jun N-terminal kinase (JNK) activation in TNBC cells. In vivo, daily intraperitoneal injection of a single dose of ZFP-B34 effectively inhibits the growth of 4T1 allografts in mice. In conclusion, ZFP-B34 is capable of inhibiting SphK1/2 and delaying the growth of TNBC cells both in vitro and in vivo.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 8","pages":"1172-1184"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793394","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":"Surface Texture Influences Environmental Preference and Locomotion in Behaving Rats.","authors":"Ryosuke Yoshida, Kotaro Yamashiro, Yuji Ikegaya, Nobuyoshi Matsumoto","doi":"10.1248/bpb.b25-00094","DOIUrl":"https://doi.org/10.1248/bpb.b25-00094","url":null,"abstract":"<p><p>In rodents, the whiskers and paws are essential for somatosensory perception, yet their preference for specific textures remains unclear. Here, we examined the preference for rough versus smooth surfaces in rats using a custom open-field paradigm with a water-based motivator to ensure consistent and unbiased movement. We found that rats strongly preferred rough textures with longer interactions and increased dwell time. Notably, this preference persisted in darkness, confirming the tactile, but not visual, influence. These findings highlight the primacy of tactile input in behavioral choices and provide key insights into optimizing rodent environments.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"825-829"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274181","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":"Validation of Risk Prediction System for Denosumab-Induced Hypocalcemia with an External Clinical Dataset.","authors":"Keisuke Ikegami, Masami Tsuchiya, Shungo Imai, Yukiyoshi Fujita, Osamu Yasumuro, Hayato Kizaki, Ryohkan Funakoshi, Yasunori Sato, Satoko Hori","doi":"10.1248/bpb.b24-00768","DOIUrl":"https://doi.org/10.1248/bpb.b24-00768","url":null,"abstract":"<p><p>Denosumab is used to reduce skeletal-related events such as fractures in cancer patients with bone metastasis, but may cause severe hypocalcemia. We previously developed and updated a risk prediction model for ≥ grade 2 denosumab-induced hypocalcemia from a hospital-based administrative database and clinical datasets from two facilities. The final risk-scoring system using only calcium, albumin, and alkaline phosphatase levels provided high performance. Here, we aimed to externally validate the scoring system's performance using an independent clinical dataset from Gunma Prefectural Cancer Center. Clinical data (May 2017-November 2023) were retrospectively collected and the discriminant performance of the previously developed model (sensitivity, specificity, positive predictive value, negative predictive value and receiver operating characteristic-area under the curve (ROC-AUC)) was evaluated. For 161 cases analyzed, the model demonstrated a sensitivity of 85.7%, specificity of 72.1%, positive predictive value of 12.2%, and negative predictive value of 99.1%. ROC-AUC was 0.813. All performance parameters were comparable to those in the previous study. The results strongly support the generalizability of the scoring system. This straightforward, easily interpretable, high-performance risk prediction system is expected to enhance the safety of denosumab treatment.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"860-863"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324448","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":"In Silico Binary Classification of Catalytic Function (Unaffected or Impaired) of Flavin-Containing Monooxygenase 3 (FMO3) Variants and in Vitro Validation Using New Variants Found in a Japanese Genome Resource Database.","authors":"Makiko Shimizu, Eiji Hishinuma, Rika Igarashi, Sakae Saito, Miaki Makiguchi, Masahiro Hiratsuka, Hiroshi Yamazaki","doi":"10.1248/bpb.b25-00359","DOIUrl":"10.1248/bpb.b25-00359","url":null,"abstract":"<p><p>Functionally impaired human flavin-containing monooxygenase 3 (FMO3) variants are associated with metabolic trimethylaminuria. The present study predicted the level of impairment of catalytic function of eight FMO3 variants newly detected in the updated Tohoku Medical Megabank. Catalytic function was modeled using the in vitro intrinsic trimethylamine N-oxygenation activities of 108 FMO3 variants using a logistic linear regression model. FMO3 proteins with single, double, triple, and quadruple amino acid variants underwent binary classification as unaffected (score 0) or impaired (≤70% of wild-type FMO3, score 1) based on their trimethylamine N-oxygenation activities. Using a model with the sum of the coefficients before and after amino acid substitutions, the mean probabilities of 62 FMO3 variants with impaired catalytic activities (0.78) were significantly higher than those of 46 with unaffected catalytic activities (0.30) (p < 0.01). The area under the corresponding receiver operating characteristic curve was 0.91. This in silico evaluation was applied to eight FMO3 variants (p.Met82Thr, p.Gly180Val, p.Ile212Leu, p.Asn275Ile, p.Gly276Glu, p.Ala377Asp, p.Tyr469Cys, and p.Val502Gly) newly found in the Tohoku Medical Megabank and validated in vitro. The present model could prove useful for estimating the activities of new FMO3 variants by applying a logistic linear regression model based on in vitro-generated catalytic data.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 7","pages":"1062-1069"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681860","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 an ESR-Based Diagnostic Probe for Matrix Metalloproteinase Activity Using a Spin-Labeled Peptide-Conjugated Styrene-Maleic Acid Copolymer.","authors":"Masato Sasaki, Kyouka Kato, Yuhei Ohta, Haruka Nakamura, Akihiko Kuniyasu, Shoko Okazaki, Keizo Takeshita","doi":"10.1248/bpb.b25-00222","DOIUrl":"https://doi.org/10.1248/bpb.b25-00222","url":null,"abstract":"<p><p>Matrix metalloproteinases (MMPs), specifically MMP-2 and MMP-9, play a significant role in tumor growth and malignancy. Therefore, measuring their activity in vivo could enhance the diagnosis and treatment of cancer. Given the medical and pharmaceutical applications of the in vivo ESR techniques in recent decades, we developed a probe to evaluate MMP activity based on ESR spectral changes that depend on the rotational correlation time of the nitroxyl radical. The probe was synthesized by conjugating the nitroxyl radical to a styrene-maleic acid copolymer via an MMP substrate peptide and polyetheramine. The ESR signal of the probe was broadened by complex formation with bovine serum albumin. When either MMP-2 or MMP-9 was added to the complex, the intensity of the sharp signal increased markedly over time. This increase was completely inhibited by specific inhibitors of MMP-2/MMP-9 and did not occur with a probe containing scrambled substrate peptides. The specific constant (k<sub>cat</sub>/K<sub>m</sub>) for degradation of the complex by MMP-2 was 4.7 × 10<sup>3</sup> M<sup>-1</sup> s<sup>-1</sup>, comparable to or 1-2 orders of magnitude lower than that of previously reported MMP-2 substrates designed for cancer therapy and diagnosis. This lower catalytic efficiency was attributed to a higher Michaelis-Menten constant relative to other MMP-2 substrates, suggesting a reduced substrate binding affinity. Despite the need for improved probe affinity, this study demonstrates a mechanism in which ESR signals increase in response to MMP-2 and MMP-9 activity, highlighting its potential for noninvasive in vivo assessment of MMP activity.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 7","pages":"1056-1061"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681858","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":"Pharmacological Inhibition of RORγ Ameliorates Skin Inflammation Induced by Both Antigen- and Cytokine-Activated Th17 Cells.","authors":"Kojo Arita, Mitsuru Tajima, Kazuma Kobayashi, Yukari Kimoto, Yusuke Kemmochi, Yoshihisa Okamoto, Yoshiaki Katsuda, Noriko Konishi, Takayuki Yamaguchi","doi":"10.1248/bpb.b25-00250","DOIUrl":"https://doi.org/10.1248/bpb.b25-00250","url":null,"abstract":"<p><p>Psoriasis is a chronic skin disease, and its symptoms markedly decrease patients' QOL. The detailed pathogenesis of psoriasis remains unclear, but previous reports about biologics targeting T helper type 17 (Th17)-related cytokines and autoantigens have suggested that both antigen- and cytokine-activated Th17 cells have important roles. Since retinoid-related orphan receptor-γ (RORγ) is recognized as the key master regulator of Th17 cells, we assessed the effects of pharmacological inhibition of RORγ using JTE-151, a novel orally available RORγ antagonist, on the activation of Th17 cells by antigen and cytokine. JTE-151 suppressed the production of both interleukin-17A (IL-17A) and IL-22 induced by myelin oligodendrocyte glycoprotein (35-55) peptide (MOG)-stimulated Th17 cells in vitro, whereas anti-IL-12/IL-23 p40 antibody did not. Moreover, JTE-151 also suppressed the production of both IL-17A and IL-22 induced by IL-23-stimulated Th17 cells in vitro. Furthermore, JTE-151 suppressed MOG-induced ear swelling in MOG-immunized mice and ameliorated IL-23-induced dermatitis in mice through the inhibition of Th17 cell activation. Taken together, we showed that pharmacological inhibition of RORγ by JTE-151 suppressed the activation of Th17 cells induced by both antigen and cytokine, and that it also ameliorated skin inflammation following Th17 cell activation. These results suggest that RORγ antagonists, including JTE-151, have the potential to become drug candidates for fighting psoriasis and other Th17-related autoimmune diseases, and that pharmacological inhibition of RORγ may also have broader effects than Th17-related cytokine-specific biological agents.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 7","pages":"1040-1048"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681861","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}
Christine Li Mei Lee, Yasunari Kanda, Sachiko Yoshida
{"title":"Prenatal Acetamiprid Exposure Enhances Microglial Activation in Primary Microglia Culture.","authors":"Christine Li Mei Lee, Yasunari Kanda, Sachiko Yoshida","doi":"10.1248/bpb.b25-00213","DOIUrl":"https://doi.org/10.1248/bpb.b25-00213","url":null,"abstract":"<p><p>Prenatal exposure to environmental chemicals, including pesticides, has been epidemiologically linked to neurodevelopmental disorders. Acetamiprid, a nicotine-mimetic insecticide, has been shown to cause neurotoxicity and abnormal neuronal distribution in rats. Furthermore, acetamiprid has been reported to activate microglia, the resident immune cells of the central nervous system, via a transition to an amoeboid shape with increased phagocytic activity in prenatally exposed neonatal mice. However, the impact of prenatal exposure to acetamiprid on offspring's microglial morphology and function remains inadequately understood. Here, we investigated the effects of prenatal exposure to acetamiprid on offspring microglial morphology and phagocytic function in response to ATP, which is released from distressed cells and results in microglial activation. We found that acetamiprid-exposed microglia significantly increased interleukin-1β (IL-1β) levels in both conditions, without and with ATP stimulation compared to microglia derived from offspring that were prenatally exposed to dimethyl sulfoxide or non-treated. In addition, microglia from offspring prenatally exposed to acetamiprid underwent morphological changes upon ATP stimulation. Given that elevated IL-1β levels are often accompanied by changes in phagocytic function, we next assessed phagocytosis under the same conditions. While phagocytosis was enhanced in the offspring prenatally exposed to acetamiprid, ATP failed to further induce phagocytic function. These findings suggest that prenatal exposure to acetamiprid enhances microglial activity but impairs the phagocytotic reactivity of offspring microglia to ATP stimulation. Further studies are needed to clarify the underlying mechanisms and potential neurodevelopmental consequences in humans.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 7","pages":"1001-1007"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625355","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":"Seasonal Variations in Drug-Related Erythema Multiforme: A Time Series Analysis Using the JADER Database.","authors":"Hideyuki Tanaka, Mika Maezawa, Sakiko Hirofuji, Koumi Miyasaka, Satoshi Nakao, Yuka Nokura, Moe Yamashita, Nanaka Ichihara, Kana Sugishita, Tomofumi Yamazaki, Kohei Shiota, Hirofumi Tamaki, Hiroyuki Tanaka, Kazuhiro Iguchi, Mitsuhiro Nakamura","doi":"10.1248/bpb.b25-00038","DOIUrl":"https://doi.org/10.1248/bpb.b25-00038","url":null,"abstract":"<p><p>Erythema multiforme (EM) is a rare, immune-mediated skin condition triggered primarily by infections, drugs, and autoimmune diseases. Although its seasonal variations have been reported, with peaks in spring and summer, comprehensive analyses remain limited. In this study, we aimed to investigate the seasonal patterns and drug associations of EM using the Japanese Adverse Drug Event Report database. A time series analysis was performed using EM-related adverse event onset dates reported between January 2005 and December 2019. The periodic patterns and residual autocorrelation were evaluated by applying seasonal and trend decomposition using loess (STL) and autocorrelation function (ACF) analyses to the time series data of monthly EM reports. A total of 3843 cases of EM were analyzed, with 43.1% being male and 56.3% female. STL decomposition identified June as the peak month for EM cases, with a higher incidence observed from spring to summer than in winter. Male patients exhibited greater seasonal variations, with a higher incidence in summer. Reports of anti-infective and antineoplastic drugs increased from spring to summer and declined in winter in male patients with EM, suggesting a potential seasonal trend. Female patients with EM also showed seasonal variations, albeit less pronounced than in male patients. The current study identified seasonal variations in drug-related EM, with reports peaking in June, which is consistent with previous observations of higher EM incidence in spring and summer. The findings indicated potential sex-related disparities in drug-related EM, underscoring the necessity for additional research to elucidate its mechanisms and patterns.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 7","pages":"1022-1030"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648428","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}
Hui-Hsin Cheng, Ming-Che Liu, Chih-Han Lin, Shu-Yu Kuo
{"title":"Integrated Clinical Trial Management System: Establishment and Efficiency Assessment.","authors":"Hui-Hsin Cheng, Ming-Che Liu, Chih-Han Lin, Shu-Yu Kuo","doi":"10.1248/bpb.b25-00110","DOIUrl":"https://doi.org/10.1248/bpb.b25-00110","url":null,"abstract":"<p><p>In the hospital settings, performing clinical trials is an intricate process that is generally hampered by several institutional, technical, and record-keeping challenges. Hence, we evaluated the effectiveness and efficiency of our established integrated clinical trial management system (CTMS) in terms of analyzing core functionalities, assessing integration with existing systems, measuring time, and cost efficiency. Our CTMS (version 10.1, August 2024) is integrated into one of the largest teaching hospitals with the human research audit system, biobank management system, biological sample management system, enterprise resource system service, institutional review, and single sign-on system. The total number of trials, subjects enrolled, products developed, investigators, new drug and indication, devices, and new medical technology are found to be 913, 53969, 851, 159, 784, and 98, respectively, with a total budget of 3539846777 New Taiwan Dollar (approx. 106881045 US$). Our CTMS is efficient in updating data, with improved user interface experience, and controlled access according to the defined policy. Integrating CTMS with other components provides effective tracking and monitoring of the clinical study. Conclusively, our integrated CTMS is designed for comprehensive evaluation and supervision of clinical trials, supporting full-process data management and seamless integration with clinical systems of hospitals through a unified interface. The increasing number of trials, subjects enrolled, products developed, investigators, new drugs and indications, devices, and new medical technology indicates its robustness and efficacy.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"782-790"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224122","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}
Jiayi Li, Tian Xiang Gao, Jun Tomita, Kazuhiko Kume
{"title":"Ameliorative Effects of Sweeteners on a Mouse Jet Lag Model.","authors":"Jiayi Li, Tian Xiang Gao, Jun Tomita, Kazuhiko Kume","doi":"10.1248/bpb.b25-00047","DOIUrl":"https://doi.org/10.1248/bpb.b25-00047","url":null,"abstract":"<p><p>Circadian rhythms regulate essential physiological functions, including body temperature and hormone secretion, in a 24-h cycle. These rhythms are synchronized with environmental cues, primarily light, through the suprachiasmatic nucleus. Disruptions, such as jet lag, misalign internal rhythms with external time, leading to fatigue and insomnia. This study explores the potential of dietary sweetening agents as non-pharmacological interventions to facilitate circadian re-entrainment in a mouse jet lag model. Male C57BL/6 mice, maintained on a 12-h light/dark cycle, underwent a 6-h phase advance to simulate jet lag. Mice received drinking water with or without sweeteners (sucrose, sucralose, xylitol, maltitol), and locomotor activity was assessed using wheel-running behavior and intraperitoneally implanted nanotags measuring 3dimensional acceleration and body temperature. Sucrose and sucralose significantly accelerated re-entrainment, with phase-shifting rates of 0.93 and 1.28 h/d, respectively, compared to 0.76 h/d in controls. Both sweeteners also enhanced post-shift activity, whereas xylitol had a minor effect and maltitol showed no significant impact. Sweeteners did not affect rest duration during the jet lag period. These findings indicate that sweet taste can facilitate circadian adaptation, offering a potential dietary approach to mitigate jet lag symptoms. This study provides insights into how taste perception influences circadian regulation, with implications for managing circadian misalignment in frequent travelers and shift workers.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"919-927"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504814","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}