Yentl Huybrechts, Raphaël De Ridder, Dylan Bergen, Björn De Samber, Eveline Boudin, Francesca Tonelli, Dries Knapen, Lucia Vergauwen, Dorien Schepers, Evelien Van Dijck, Qiao Tong, Anja Verhulst, Jan De Beenhouwer, Jan Sijbers, Chrissy Hammond, Antonella Forlino, Geert Mortier, Paul Coucke, P Eckhard Witten, Ronald Young Kwon, Andy Willaert, Gretl Hendrickx, Wim Van Hul
{"title":"Loss of the Ubiquitin-Associated Domain of sqstm1/p62 in Zebrafish Causes a Phenotype Resembling Paget's Disease of Bone.","authors":"Yentl Huybrechts, Raphaël De Ridder, Dylan Bergen, Björn De Samber, Eveline Boudin, Francesca Tonelli, Dries Knapen, Lucia Vergauwen, Dorien Schepers, Evelien Van Dijck, Qiao Tong, Anja Verhulst, Jan De Beenhouwer, Jan Sijbers, Chrissy Hammond, Antonella Forlino, Geert Mortier, Paul Coucke, P Eckhard Witten, Ronald Young Kwon, Andy Willaert, Gretl Hendrickx, Wim Van Hul","doi":"10.1007/s00223-025-01360-2","DOIUrl":"10.1007/s00223-025-01360-2","url":null,"abstract":"<p><p>The ubiquitin-binding protein p62, encoded by Sequestosome 1 (SQSTM1), is an essential molecular adaptor for selective autophagy. Heterozygous mutations deleting or disrupting the ubiquitin-associated (UBA) domain of p62 have been reported as the major genetic cause for Paget's disease of bone (PDB), the second most common skeletal disease, characterized by hyperactive osteoclasts and focal increases of bone turnover. In this study, we aimed to determine the impact of a similar sqstm1/p62 mutation on the skeleton of zebrafish. We successfully established a sqstm1<sup>tmΔUBA</sup> zebrafish line with premature truncation of the UBA domain and performed skeletal phenotyping of heterozygous and homozygous mutant zebrafish. Homozygous sqstm1<sup>tmΔUBA</sup> zebrafish suffered from early lethality after 6 mpf, possibly related to a dysregulated autophagy process. Nevertheless, we detected skeletal abnormalities that were generally more severe in older animals and in homozygous versus heterozygous sqstm1<sup>tmΔUBA</sup> zebrafish. MicroCT analysis and histologic staining showed alterations in the vertebral bodies and/or bone density in heterozygous sqstm1<sup>tmΔUBA</sup> zebrafish. We also detected signs of osteocytic osteolysis in carriers of a mutant sqstm1<sup>tmΔUBA</sup> allele, shown by a higher percentage of enlarged osteocyte lacunae at 12mpf (36% in heterozygote mutants, 20% in wild types). By performing scale histomorphometry, we also detected a higher degree of scale resorption in homozygous sqstm1<sup>tmΔUBA</sup> zebrafish at 6 mpf. In conclusion, we have generated a Sqstm1 mutant zebrafish model with features of PDB, characterized by focal bone defects and increased osteoclast activity. This model may be useful to further define PDB disease mechanisms and other p62-related (patho)physiological processes.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"52"},"PeriodicalIF":3.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630204","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":"Prevalence of Comorbid Hyperparathyroidism and Its Association with Renal Dysfunction in Asian Patients with X-Linked Hypophosphatemic Rickets/Osteomalacia.","authors":"Nobuaki Ito, Hee Gyung Kang, Toshimi Michigami, Noriyuki Namba, Takuo Kubota, Ayumi Shintani, Ryota Kawai, Daijiro Kabata, Haruka Ishii, Yayoi Nishida, Seiji Fukumoto, Keiichi Ozono","doi":"10.1007/s00223-025-01359-9","DOIUrl":"10.1007/s00223-025-01359-9","url":null,"abstract":"<p><p>In patients with X-linked hypophosphatemic rickets/osteomalacia (XLH) in Asia, the current prevalence of hyperparathyroidism and its association with renal dysfunction have not been determined. We used patient data retrospectively collected up to the time of informed consent in the SUNFLOWER study, a long-term observational study, to investigate the current treatment status and prevalence of comorbid hyperparathyroidism and its association with renal dysfunction in patients with XLH in Japan and South Korea. Of 69 patients who met the eligibility criteria, 32 (46.4%) did not have hyperparathyroidism (hereinafter referred to as non-hyperparathyroidism), 33 (47.8%) had secondary hyperparathyroidism, and four (5.8%) had tertiary hyperparathyroidism. Men were more prone to develop secondary and tertiary hyperparathyroidism, use oral phosphate at higher frequencies, and have a higher incidence of Stage ≥ 3 chronic kidney disease and Grade ≥ 3 renal calcification than women. Ongoing treatments for patients with XLH and non-hyperparathyroidism, secondary hyperparathyroidism, and tertiary hyperparathyroidism mainly consisted of active vitamin D (30 [93.8%], 25 [75.8%], and 3 [75.0%], respectively) and oral phosphate (21 [65.6%], 23 [69.7%], and 4 [100.0%], respectively). At informed consent, patients with tertiary hyperparathyroidism had the lowest estimated glomerular filtration rate values. Our study highlights the prevalence of comorbid hyperparathyroidism and its association with renal dysfunction in patients with XLH through a large-scale observational study in Asia.Trial registration: NCT03745521; UMIN000031605.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"50"},"PeriodicalIF":3.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613472","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}
Yamei Liu, Xiaoqi Deng, Chen Chen, Binlan Fu, Min Wang, Jinglan Li, Liangliang Xu, Bin Wang
{"title":"Atractylenolide I Attenuates Glucocorticoid-Induced Osteoporosis via Inhibiting NF-κB Signaling Pathway.","authors":"Yamei Liu, Xiaoqi Deng, Chen Chen, Binlan Fu, Min Wang, Jinglan Li, Liangliang Xu, Bin Wang","doi":"10.1007/s00223-025-01358-w","DOIUrl":"10.1007/s00223-025-01358-w","url":null,"abstract":"<p><p>Long-term treatment with glucocorticoids significantly impacts bone health, with glucocorticoid-induced osteoporosis (GIOP) being the most prevalent consequence. Previous studies have established that Atractylenolide I (Atr I) possesses anti-inflammatory, antioxidant and anti-tumor properties, however, its specific effects on osteoclastogenesis and GIOP are still unclear. In this study, our in vitro results revealed that Atr I inhibited RANKL-stimulated osteoclast differentiation in a dose-dependent manner, disrupted the structure of the F-actin belt in mature osteoclasts, blocked RANKL-induced ROS production, and suppressed the expression of osteoclast-associated genes. Mechanistically, the findings indicated that Atr I inhibited the RANKL-induced activation of the NF-κB signaling pathway. In vivo, the micro-CT, bone histomorphometric analysis and histological data demonstrated that Dex administration led to significant bone loss, accompanied by a considerable increase in the number of osteoclasts on the bone surface. Conversely, treatment with Atr I effectively prevented these Dex-induced alterations. Taken together, this study suggests that Atr I may hold potential as a therapeutic agent for the treatment of GIOP.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"51"},"PeriodicalIF":3.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613470","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}
Yan Wang, Duoshan Ma, Chunyu Wang, Xinxin Zhang, Mengna Tang, Jishuai Hu, Faxiang Li, Jianbo Gao, Yan Wu
{"title":"The Relationship Between the Heterogeneity of Lumbar Vertebral Trabecular Bone Mineral Density Distribution and Osteoporotic Vertebral Fractures.","authors":"Yan Wang, Duoshan Ma, Chunyu Wang, Xinxin Zhang, Mengna Tang, Jishuai Hu, Faxiang Li, Jianbo Gao, Yan Wu","doi":"10.1007/s00223-025-01342-4","DOIUrl":"10.1007/s00223-025-01342-4","url":null,"abstract":"<p><p>This study aims to investigate the relationship between the spatial distribution and heterogeneity of lumbar vertebral trabecular volumetric bone mineral density (vBMD) and osteoporotic vertebral fractures(OVF). This retrospective study included the L1 and L2 vertebrae of 143 participants with osteoporotic vertebral fractures and 429 age- and sex-matched no-fractured controls. Spatial distribution was assessed using the superior/middle and inferior/middle ratios, while heterogeneity was indicated by the quartile coefficient of variation (QCV) and interquartile range (IQR). We used QCT to measure the integral vBMD of the vertebra and the regional vBMD in the superior, middle, and inferior subregions. QCV and IQR were computed for both integral vertebrae and three subregions using voxel values from CT images. Differences between fracture and control groups were analyzed after stratification by age and sex. T-tests and Wilcoxon rank-sum tests assessed differences in spatial distribution and heterogeneity between fracture and control groups. Conditional logistic regression was employed to evaluate the associations between spatial distribution and heterogeneity with osteoporotic vertebral fractures. Trabecular vBMD was higher in the middle subregion of the vertebrae than the superior and inferior subregions. The fracture group had lower mean integral vBMD than controls. In terms of the spatial distribution, significant differences in the superior/middle and inferior/middle ratios of the L1 vertebra were observed between the fracture and control groups in the female 40-60 years group. The superior/middle ratio of the L1 vertebra in males was positively correlated with the fracture risk. Regarding heterogeneity, the fracture group had a higher QCV than the control group. QCV was positively correlated with fracture risk, with no significant variation between sexes. The spatial distribution and heterogeneity of trabecular vBMD are crucial for predicting vertebral fracture risk. These indicators are essential for fracture risk assessment and may inform prevention and treatment strategies.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"49"},"PeriodicalIF":3.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604014","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}
Aaron P Robertson, Brendan J Jones, Christian M Langton, Scott C Wearing
{"title":"Calcaneal Ultrasound Attenuation: Does the Region of Interest and Loading Influence the Repeatability of Measurement?","authors":"Aaron P Robertson, Brendan J Jones, Christian M Langton, Scott C Wearing","doi":"10.1007/s00223-025-01357-x","DOIUrl":"10.1007/s00223-025-01357-x","url":null,"abstract":"<p><p>Current calcaneal quantitative ultrasound systems assess different regions of interest (ROI), under different levels of lower limb loading, yield different parameter values, and are likely prone to different levels of error. This study evaluated the repeatability of measures of frequency-dependent attenuation (FDA, 0.3-0.8 MHz) at three calcaneal ROI, Brooke-Wavell (BW), Jaworski (JA), and foot gauge (FG), under four loading conditions (non-weightbearing, semi-weightbearing, bipedal stance, and unipedal stance). FDA in the calcaneus was assessed in 20 healthy participants (mean (± SD) age, 41.7 ± 19.6 years; height, 1.70 ± 0.16 m; and weight, 70.1 ± 23.0 kg) using a custom-built transmission-mode ultrasound system. Reliability was evaluated using the standard error of measurement (SEM) and limits of agreement (LA) and tolerance (95%TL). Differences in mean FDA values between ROI, loading, and measurement occasions were assessed using a repeated measures ANOVA (α = .05). Mean FDA values ranged between 58.0 ± 32.0 and 77.2 ± 27.6 dB/MHz across all conditions. Repeatability of FDA was dependent on the ROI examined and tended to improve with weightbearing. The narrowest limits for 95%TL ranged between ± 15.1 dB/MHz (JA SWB) and ± 62.7 dB/MHz (BW NWB) across sites. The SEM was approximately 10 dB/MHz for both FG and JA during non-weightbearing and was reduced to around 5 dB/MHz with full weightbearing. This study demonstrates that, although measures of ultrasound FDA are dependent on the ROI, lower limb loading may be a useful method to improve the repeatability of FDA measurements.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"48"},"PeriodicalIF":3.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584731","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":"Efficacy and Safety of Bisphosphonates in Chronic Non-bacterial Osteomyelitis of the Mandible: A Systematic Review.","authors":"Debraj Howlader, Dipti Daga, Abanti Das, Ritasman Baisya, Bhupendra Babaria","doi":"10.1007/s00223-025-01354-0","DOIUrl":"10.1007/s00223-025-01354-0","url":null,"abstract":"<p><p>Chronic non-bacterial osteomyelitis (CNO) of the mandible, often called diffuse sclerosing osteomyelitis (DSO) in Maxillofacial and Dental literature, is a rare condition characterized by sterile osteomyelitis affecting the mandible. This condition is part of the chronic recurrent multifocal osteomyelitis (CRMO)/synovitis, acne, pustulosis, hyperostosis, and osteomyelitis (SAPHO) spectrum. However, because mandibular involvement may present as unifocal disease, it deserves special attention. Unfortunately, the rarity of this disorder, along with a general lack of awareness, has led to numerous unnecessary and ineffective surgical interventions in the past. While some of these lesions may resolve on their own with only symptomatic management with NSAIDs, there is increasing evidence that lesions refractory to NSAIDs can respond well to bisphosphonates (BPNs). The authors conducted a systematic review following PRISMA guidelines to investigate the effectiveness of BPNs for CNO/SAPHO of the mandible and to assess potential adverse reactions, particularly medication-related osteonecrosis of the jaw (MRONJ). In this review, we identified one randomized controlled trial and nine case series describing the use of bisphosphonates in treating mandibular CNO/SAPHO. While heterogeneity among the studies precluded the extraction of statistically relevant information, BPNs are an effective treatment for mandibular CNO with minimal chance of jaw osteonecrosis and disturbance to the growing skeleton.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"47"},"PeriodicalIF":3.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584734","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}
L Seefried, F Genest, C Hofmann, M L Brandi, E Rush
{"title":"Diagnosis and Treatment of Hypophosphatasia.","authors":"L Seefried, F Genest, C Hofmann, M L Brandi, E Rush","doi":"10.1007/s00223-025-01356-y","DOIUrl":"10.1007/s00223-025-01356-y","url":null,"abstract":"<p><p>Hypophosphatasia (HPP) is a rare inherited metabolic disorder characterized by deficient activity of tissue-nonspecific alkaline phosphatase (TNAP) caused by variants in the ALPL gene. Disease manifestations encompass skeletal hypomineralization with rickets and lung hypoplasia, vitamin B6-dependent seizures, craniosynostosis, and premature loss of deciduous teeth. The clinical presentation can comprise failure to thrive with muscular hypotonia, delayed motor development, and gait disturbances later in childhood. In adults, pseudofractures are a characteristic indicator of severely compromised enzyme activity, but non-canonical symptoms like generalized musculoskeletal pain, weakness, and fatigue, frequently accompanied by neuropsychiatric and gastrointestinal issues are increasingly recognized as key findings in patients with HPP. The diagnosis is based on clinical manifestations in combination with persistently low alkaline phosphatase (ALP) activity, elevated levels of ALP substrates, specifically inorganic pyrophosphate (PPi), pyridoxal 5'-phosphate (PLP) or urine phosphoethanolamine (PEA), and genetic confirmation of a causative ALPL variant. Considering the wide range of manifestations, treatment must be multimodal and tailored to individual needs. The multidisciplinary team for comprehensive management of HPP patients should include expertise to ensure disease state metabolic and musculoskeletal treatment, dental care, neurological and neurosurgical surveillance, pain management, physical therapy, and psychological care. Asfotase alfa as first-in-class enzyme replacement therapy (ERT) for HPP has been shown to improve survival, rickets, and functional outcomes in severely affected children, but further research is needed to refine how enzyme replacement can also address emerging manifestations of the disease. Prospectively, further elucidating the pathophysiology behind the diverse clinical manifestations of HPP is instrumental for improving diagnostic concepts, establishing novel means for substituting enzyme activity, and developing integrative, multimodal care.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"46"},"PeriodicalIF":3.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566016","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}
P R Gokul, C Jarvis, G Kassab, S Armitage, M Z Mughal, D Hughes, R Ramakrishnan
{"title":"Correction to: Base of Skull & Spinal Canal Narrowing in an Adolescent with Autosomal Recessive Hypophosphatemic Rickets Type 2.","authors":"P R Gokul, C Jarvis, G Kassab, S Armitage, M Z Mughal, D Hughes, R Ramakrishnan","doi":"10.1007/s00223-025-01353-1","DOIUrl":"https://doi.org/10.1007/s00223-025-01353-1","url":null,"abstract":"","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"45"},"PeriodicalIF":3.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540276","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}
Sandra Baumann, Lilian Sewing, Cyril Traechslin, Wilma Verhagen-Kamerbeek, Leticia Grize, Marius Kraenzlin, Christian Meier
{"title":"Correction to: Serum Pentosidine in Relation to Obesity in Patients with Type 2 Diabetes and Healthy Controls.","authors":"Sandra Baumann, Lilian Sewing, Cyril Traechslin, Wilma Verhagen-Kamerbeek, Leticia Grize, Marius Kraenzlin, Christian Meier","doi":"10.1007/s00223-025-01352-2","DOIUrl":"10.1007/s00223-025-01352-2","url":null,"abstract":"","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"44"},"PeriodicalIF":3.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482370","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":"Semaphorin 3A on Osteoporosis: An Overreview of the Literature.","authors":"Yueyi Zhang, Hanfen Shi, Xuan Dai, Jin Shen, Jiyuan Yin, Tianshu Xu, Gaiyue Yue, Haochen Guo, Ruiqiong Liang, Qishuang Chen, Sihua Gao, Lili Wang, Dongwei Zhang","doi":"10.1007/s00223-025-01350-4","DOIUrl":"10.1007/s00223-025-01350-4","url":null,"abstract":"<p><p>Semaphorin 3A (Sema3A) is a signaling protein that has attracted increasing attention in recent years for its important role in regulating bone metabolism. In this review, we searched different databases with various combinations of keywords to analyze the effects of Sema3A on osteoporosis. Sema3A promotes bone formation and inhibits bone resorption by directly affecting the osteoblast and osteoclast or indirectly targeting the nervous system. The sympathetic nervous system may be the main link between the central nervous system and bone metabolism for Sema3A. In the peripheral nervous system, Sema3A may improve bone quality via sensory nervous innervation. In addition, estrogen is found to regulate Sema3A levels to improve bone homeostasis. Lots of Sema3A agonists have been documented to exhibit anti-osteoporotic potential in preclinical investigations. Therefore, Sema3A can be considered a novel therapeutic target for preserving bone mass, highlighting an alternative strategy for the development of anti-osteoporosis drugs.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"43"},"PeriodicalIF":3.3,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476432","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}