{"title":"Hck promotes IL-1β-induced extracellular matrix degradation, inflammation, and apoptosis in osteoarthritis via activation of the JAK-STAT3 signaling pathway.","authors":"Zhenzhong Yan, Lin Ji","doi":"10.1186/s42358-024-00427-2","DOIUrl":"https://doi.org/10.1186/s42358-024-00427-2","url":null,"abstract":"<p><p>We investigated role of haematopoietic cell kinase (Hck) in osteoarthritis (OA) and to explore the underlying mechanisms driving its effects. An OA animal model was established and after OA induction, rats received intra-articular injections of lentivirus twice a week for four weeks. Rats were divided into four groups: control (healthy rats without OA), OA model (rats with induced OA), OA + Len-si-NC (OA rats treated with a non-targeting control lentivirus), and OA + Len-si-Hck (OA rats treated with lentivirus targeting Hck). Blood samples were collected, and serum cytokine levels were measured using ELISA. Afterward, the rats were sacrificed for histological analysis and TUNEL assay. In vitro, IL-1β-treated human chondrocytes were transfected with Hck, and the effects on cell viability, apoptosis, ECM degradation, and JAK-STAT3 signaling were assessed. Colivelin, a JAK-STAT3 agonist, was used to confirm the pathway's involvement. Results indicated increased Hck expression in the cartilage tissues of OA rats and in IL-1β-stimulated chondrocytes. Silencing Hck in vivo reduced IL-6 and TNF-α levels, apoptosis, and preserved cartilage structure. In vitro, Hck knockdown in IL-1β-treated chondrocytes resulted in enhanced cell viability, reduced apoptosis, and decreased ECM degradation. Notably, the expression of MMP3 and MMP13 was significantly lowered, while collagen II and aggrecan levels were restored. Additionally, Hck knockdown inhibited JAK-STAT3 activation, which was evident from reduced levels of phosphorylated JAK1 and STAT3. The addition of colivelin reversed these effects, confirming that Hck mediates its effects through the JAK-STAT3 pathway. Overall, our findings indicate that Hck is critical in OA progression by promoting inflammation, apoptosis, and ECM degradation through the JAK-STAT3 signaling pathway activation.</p>","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":"64 1","pages":"88"},"PeriodicalIF":2.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856267","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}
Ziming Geng, Yang Tong, Yang Chen, Jian Wang, Ziwen Liu, Jun Miao, Ruihua Li
{"title":"Investigating the causal relationship between immune factors and ankylosing spondylitis: insights from a Mendelian Randomization study.","authors":"Ziming Geng, Yang Tong, Yang Chen, Jian Wang, Ziwen Liu, Jun Miao, Ruihua Li","doi":"10.1186/s42358-024-00428-1","DOIUrl":"https://doi.org/10.1186/s42358-024-00428-1","url":null,"abstract":"<p><strong>Background: </strong>Despite previous studies indicating a close relationship between immune system and ankylosing spondylitis (AS), the causal relationship between them remains unclear.</p><p><strong>Methods: </strong>Genome-wide association data were utilized to explore the causal link between 731 immune cells and AS using a bidirectional two-sample MR approach. The data included immune cell data from Orrù et al.'s study and AS data from the FinnGen consortium. Cochran's Q test and leave-one-out checked instrument variable (IV) heterogeneity. IVW was the primary method for causal analysis, with MR-Egger and MR-PRESSO addressing horizontal pleiotropy. FDR correction was applied to both analysis directions to rectify multiple testing errors.</p><p><strong>Results: </strong>In our study, 22 immune phenotypes out of 731 were casually linked to AS. After excluding 5 less robust features, 17 immune factors remained, with 4 being protective and the rest posing risks. Through FDR correction, we found a significant causal relationship between HLA DR on CD14- CD16+ monocyte and AS (OR (95%CI) = 0.70(0.60 ~ 0.83), P = 2.06*10<sup>-5</sup>). In the reverse analysis with AS as exposure, potential effects on 34 immune features were discovered. After correction, we confirmed significant causal relationships between AS and two immune features, namely CD20- B cell %lymphocyte (OR (95%CI) = 1.16(1.08-1.25), P = 1.91*10<sup>-5</sup>) and CD20- B cell %B cell (OR (95%CI) = 1.17(1.09-1.26), P = 1.50*10<sup>-5</sup>).</p><p><strong>Conclusions: </strong>Our study identified various features associated with AS in different types of immune cells. These findings provide important clues and a theoretical basis for further understanding the pathogenesis of AS, guiding clinical treatment, and drug design.</p>","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":"64 1","pages":"89"},"PeriodicalIF":2.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856295","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}
Thales Hein da Rosa, Bárbara Jonson Bartikoski, Rafaela Cavalheiro do Espírito Santo, Mirian Farinon, Jordana Miranda de Souza Silva, Renata Ternus Pedó, Maria Luísa Gasparini, Thais Karnopp, Leonardo Peterson Dos Santos, Gustavo Chapacais, Andressa di Domenico, Sofia Loch, Ricardo Machado Xavier
{"title":"Treatment with tofacitinib attenuates muscle loss through myogenin activation in the collagen-induced arthritis.","authors":"Thales Hein da Rosa, Bárbara Jonson Bartikoski, Rafaela Cavalheiro do Espírito Santo, Mirian Farinon, Jordana Miranda de Souza Silva, Renata Ternus Pedó, Maria Luísa Gasparini, Thais Karnopp, Leonardo Peterson Dos Santos, Gustavo Chapacais, Andressa di Domenico, Sofia Loch, Ricardo Machado Xavier","doi":"10.1186/s42358-024-00416-5","DOIUrl":"https://doi.org/10.1186/s42358-024-00416-5","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia is a muscle disease characterized by reduction of muscle strength and muscle mass. In RA, 25.9 to 43.3% of the patients present sarcopenia. The loss of muscle mass observed in RA patients occurs either by activation of catabolic pathways or by inhibition of anabolic pathways. Despite having a list of drugs capable of treating RA inflammation, their effect on muscle is unclear. Our objective was to evaluate the tofacitinib effect on the muscle mass of collagen-induced arthritis (CIA) mice.</p><p><strong>Methods: </strong>CIA was induced in male DBA/1J mice by subcutaneous injection of Type 2 Collagen plus Freund Adjuvant. Animals were randomized into 3 groups: CIA + tofacitinib; CIA + vehicle; and healthy controls. Treatment was administered twice a day, between days 18 and 45 after induction. Clinical score, edema, and body weight were evaluated during the experimental period. After euthanasia, tibiotarsal joints were collected for assessment of disease histopathological score, and tibialis anterior (TA) and gastrocnemius (GA) muscles were weighed to assess muscle mass. Muscle atrophy was evaluated by measurement of TA myofiber cross-sectional area (CSA). Protein expression was evaluated by western blot using GA homogenates. Serum inflammatory markers were evaluated by ELISA. Statistical analysis included ANOVA followed by Tukey's or with Kruskal-Wallis. The statistical difference was assumed for p < 0.05.</p><p><strong>Results: </strong>Tofacitinib treatment decreased arthritis severity by reducing clinical score, and hind paw edema in comparison with the vehicle group. Tofacitinib showed weight gain, higher TA and GA weights, and increased CSA compared to the vehicle group. On day 45, Tofacitinib presented increased muscle strength compared to the vehicle group, however, no difference was found in muscle fatigue. Pax7 expression was unchanged, while MyoD expression showed an increasing trend, and myogenin expression was significantly increased in Tofacitinib compared to vehicle and control groups. The treatment didn't modify Murf-1 expression. Tofacitinib mice showed decreased serum levels of TNF and increased IL-6 serum levels.</p><p><strong>Conclusion: </strong>Tofacitinib attenuated muscle loss in arthritic mice, increased muscle weight and muscle CSA. Activation of satellite cell regeneration, based on the increased expression of myogenin, is a potential mechanism involved in tofacitinib action against muscle loss.</p>","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":"64 1","pages":"85"},"PeriodicalIF":2.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630682","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}
Ana Luisa Souza Pedreira, Maria de Lourdes Castro de Oliveira Figueiroa, Mariana Oliveira Miranda, Alisson Regis de Santana, Victor Pereira Mattos, Adriane Sousa da Paz, Camila Cendon Duran, Mittermayer Barreto Santiago
{"title":"Takayasu's arteritis associated with tuberculosis: a retrospective study.","authors":"Ana Luisa Souza Pedreira, Maria de Lourdes Castro de Oliveira Figueiroa, Mariana Oliveira Miranda, Alisson Regis de Santana, Victor Pereira Mattos, Adriane Sousa da Paz, Camila Cendon Duran, Mittermayer Barreto Santiago","doi":"10.1186/s42358-024-00424-5","DOIUrl":"https://doi.org/10.1186/s42358-024-00424-5","url":null,"abstract":"<p><strong>Background: </strong>Takayasu arteritis (TA) and tuberculosis (TB) share similar histopathological and immunological characteristics. Studies comparing patients with TA with or without active or latent TB infection (LTBI) have revealed some differences in clinical and angiographic profiles. Patient with TA and history of TB exhibited more constitutional symptoms and structural damage to the aorta. This study compared the clinical and radiological features of patients with TA with and without active TB or LTBI.</p><p><strong>Methods: </strong>We retrospectively analyzed the data of patients with TA at a public tertiary referral outpatient clinic in northeast Brazil from January 2017 to June 2022. Comparisons of clinical features were made according to the presence of TB.</p><p><strong>Results: </strong>Fifty patients met the eligibility criteria, and a association with TB was identified in 20 (40%) patients (active TB in six and LTBI in 14). There was a predominance of females, and the average age of patients was 40 years. Weight loss was more common in patients with TA and TB (p = 0.005). No significant intergroup differences were noted in terms of comorbidities, medications, erythrocyte sedimentation rates, or C-reactive protein levels. Significant differences were found in abdominal aortic involvement (25% of patients with TA and TB vs. 11.4% in subjects with TA without TB; p = 0.013). Dilations and aneurysms were significantly more common in patients with TA and TB (p = 0.009 and p = 0.027, respectively).</p><p><strong>Conclusion: </strong>Patients with TA and TB have a higher prevalence of dilatation and aneurysms, most commonly in the abdominal aorta.</p>","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":"64 1","pages":"84"},"PeriodicalIF":2.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630662","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":"Analysis of the causal relationship between immune cells and rheumatoid arthritis from the perspective of genetic variation: a bidirectional two-sample Mendelian randomization study.","authors":"Feng Cheng, YingJia Zhu, XiaoQian Liu, RuiKun Zhang, Fei Xia, LinPu Ge","doi":"10.1186/s42358-024-00425-4","DOIUrl":"https://doi.org/10.1186/s42358-024-00425-4","url":null,"abstract":"<p><strong>Background: </strong>Immune factors are crucial in the pathogenesis of rheumatoid arthritis (RA), and immune cells play a key role in the development of RA. However, there is still disagreement regarding the specific roles of each type of immune cell in the pathological process of RA.</p><p><strong>Methods: </strong>This study used bidirectional two-sample Mendelian randomization (MR) analysis to determine the causal relationship between immune cell characteristics and RA. Utilizing publicly available genetic data, we initially treated immune cell characteristics as exposures to investigate their causal effects on the risk of RA. Subsequently, we performed reverse two-sample MR using the positively selected cells from the initial analysis as outcomes, aiming to identify the core immune cells involved. Finally, a comprehensive sensitivity analysis was conducted to validate the robustness, heterogeneity, and horizontal pleiotropy of the results.</p><p><strong>Results: </strong>Using data from 731 immune cells as exposures and cell SNPs as instruments, we independently conducted two-sample MR analysis for each patient with RA. The main analytical method used was the IVW method, with a significance level set at P < 0.05 for inclusion. In total, we identified 42 immune cell phenotypes that were causally associated with the onset of RA. For the reverse MR analysis, we used RA as the exposure factor and focused on 42 immune cell phenotypes as outcomes. Our analysis revealed causal relationships between the onset of RA and 7 immune cell phenotypes. Among these, 6 showed positive causal relationships, while 1 exhibited a negative causal relationship.</p><p><strong>Conclusions: </strong>Our study emphasized the causal relationship between immune cells and RA through bidirectional two-sample MR analysis, identifying the immune cells causally associated with RA.</p>","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":"64 1","pages":"83"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564918","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}
Edgard Torres Dos Reis-Neto, Luciana Parente Costa Seguro, Emília Inoue Sato, Eduardo Ferreira Borba, Evandro Mendes Klumb, Lilian Tereza Lavras Costallat, Marta Maria das Chagas Medeiros, Eloisa Bonfá, Nafice Costa Araújo, Simone Appenzeller, Ana Carolina de Oliveira E Silva Montandon, Emily Figueiredo Neves Yuki, Roberto Cordeiro de Andrade Teixeira, Rosa Weiss Telles, Danielle Christinne Soares do Egypto, Francinne Machado Ribeiro, Andrese Aline Gasparin, Antonio Silaide de Araujo Junior, Cláudia Lopes Santoro Neiva, Debora Cerqueira Calderaro, Odirlei Andre Monticielo
{"title":"Correction to: II Brazilian Society of Rheumatology consensus for lupus nephritis diagnosis and treatment.","authors":"Edgard Torres Dos Reis-Neto, Luciana Parente Costa Seguro, Emília Inoue Sato, Eduardo Ferreira Borba, Evandro Mendes Klumb, Lilian Tereza Lavras Costallat, Marta Maria das Chagas Medeiros, Eloisa Bonfá, Nafice Costa Araújo, Simone Appenzeller, Ana Carolina de Oliveira E Silva Montandon, Emily Figueiredo Neves Yuki, Roberto Cordeiro de Andrade Teixeira, Rosa Weiss Telles, Danielle Christinne Soares do Egypto, Francinne Machado Ribeiro, Andrese Aline Gasparin, Antonio Silaide de Araujo Junior, Cláudia Lopes Santoro Neiva, Debora Cerqueira Calderaro, Odirlei Andre Monticielo","doi":"10.1186/s42358-024-00423-6","DOIUrl":"https://doi.org/10.1186/s42358-024-00423-6","url":null,"abstract":"","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":"64 1","pages":"82"},"PeriodicalIF":2.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548384","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":"A functional exercise program improves pain and health related quality of life in patients with fibromyalgia: a randomized controlled trial.","authors":"Giovana Fernandes, Michele Nery, Sandra Mara Meireles, Rebeka Santos, Jamil Natour, Fabio Jennings","doi":"10.1186/s42358-024-00422-7","DOIUrl":"10.1186/s42358-024-00422-7","url":null,"abstract":"<p><strong>Background/objective: </strong>Fibromyalgia is a non-inflammatory syndrome characterized by generalized muscle pain, with other symptoms. Numerous forms of physical training for this population have been studied through high-quality randomized clinical trials involving strength, flexibility, aerobic conditioning and multicomponent exercise interventions. This research evaluated the effectiveness of a functional exercise program at reducing pain, improving functional capacity, increasing muscle strength as well as improving flexibility, balance and quality of life in individuals with fibromyalgia.</p><p><strong>Methods: </strong>Eighty-two women with fibromyalgia were randomized into two groups. The functional exercise group performed functional exercises in 45-minute sessions twice per week for 14 weeks. The stretching exercise group performed flexibility exercises with the same duration and frequency. Outcome measures were: visual analog scale for widespread pain; Fibromyalgia Impact Questionnaire for health-related quality of life; Timed Up and Go test for functional performance; one-repetition maximum for muscle strength, Sit and Reach test on Wells bench for flexibility; Berg Balance Scale for balance; SF-36 for general quality of life.</p><p><strong>Results: </strong>After the intervention, the functional exercise group had a statistically significant reduction in pain (interaction p = 0.002), and improvement in health-related quality of life measured by the Fibromyalgia Impact Questionnaire (interaction p < 0.001) and in general health state domain of SF-36 (interaction p = 0.043) compared to the stretching exercise group. No significant differences between groups were found regarding improvements in functional capacity, muscle strength, flexibility or balance.</p><p><strong>Conclusion: </strong>Functional exercise training was effective at reducing pain and improving quality of life in patients with fibromyalgia compared to stretching exercises.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT03682588 First prospectively registered in March 2018.</p>","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":"64 1","pages":"81"},"PeriodicalIF":4.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142510984","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":"Association of Tramadol Versus Codeine Prescriptions with all-cause mortality and cardiovascular diseases among patients with osteoarthritis: a systematic review and meta-analysis of propensity score-matched population-based cohort studies.","authors":"Mansour Bahardoust, Sepideh Mousavi, Maryam Zolfaghari Dehkharghani, Mahsa Arab, Heeva Rashidi, Habib Gorgani, Meisam Haghmoradi, Alireza Askari","doi":"10.1186/s42358-024-00417-4","DOIUrl":"10.1186/s42358-024-00417-4","url":null,"abstract":"<p><strong>Background: </strong>Today, the prescription of tramadol in patients with osteoarthritis (OA) has increased significantly, which can be associated with serious consequences. Contradictory results have been reported regarding the association of tramadol versus codeine with the risk of all-cause mortality (ACM) and cardiovascular diseases (CVD).</p><p><strong>Methods: </strong>This systematic review and meta-analysis aimed to evaluate, for the first time, the association of tramadol versus codeine with the risk of ACM and CVD in OA patients for the first time. We searched PubMed, Scopus, Embase, Web of sciences, and Google Scholar with specific keywords and mesh terms to find relevant studies until January 2024. Two independent researchers did the process of searching and screening articles. Cochran's Q and I2 tests evaluated the heterogeneity of the studies. Egger's test was used to evaluate the existence of publication bias.</p><p><strong>Results: </strong>Seven population-based cohort studies, matched by the propensity score method, including 1,939,293 participants, were reviewed. The study pooled results did not show a significant association between the prescriptions of tramadol versus codeine with increasing the risk of ACM in OA patients. (Hazard ratio (HR): 1.084, 95% confidence interval (95%) CI: 0.883, 1.286, P: 0.56) In addition, the prescription of tramadol versus codeine was not associated with an increased risk of CVD in OA. (HR: 1.025, 95% CI: 0.89, 1.16, P: 0.68, I<sup>2</sup> = 37.8%) CONCLUSION: Our systematic review showed that tramadol prescription compared to codeine in OA patients was not associated with an increased risk of ACM and CVD.</p>","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":"64 1","pages":"80"},"PeriodicalIF":2.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478194","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}
Joao Gabriel Dantas, Erika Biegelmeyer, Eduarda Bonelli Zarur, Frederico Augusto Gurgel Pinheiro
{"title":"Rare primary vasculitis: update on multiple complex diseases and the new kids on the block.","authors":"Joao Gabriel Dantas, Erika Biegelmeyer, Eduarda Bonelli Zarur, Frederico Augusto Gurgel Pinheiro","doi":"10.1186/s42358-024-00421-8","DOIUrl":"https://doi.org/10.1186/s42358-024-00421-8","url":null,"abstract":"<p><p>Systemic vasculitis is a group of rare diseases that share an essential characteristic: inflammation of blood vessel walls. This injury occurs during the disease course, but specific features vary for each entity. In this paper, we will address relevant aspects of the newest monogenic mutation vasculitis, such as deficiency of adenosine deaminase 2 (ADA2) and VEXAS syndrome (UBA1), and other relevant vasculitis, such as Cogan syndrome and Susac syndrome that may share some similarities with them.</p>","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":"64 1","pages":"79"},"PeriodicalIF":2.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394355","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}