Journal of Molecular Medicine-Jmm最新文献

{"title":"Mechanism and application of HDAC inhibitors in the treatment of hepatocellular carcinoma.","authors":"Wei Hao, Qingchen Zhang, Yuan Ma, Yue Ding, Chunling Zhao, Chunyan Tian","doi":"10.1007/s00109-025-02532-1","DOIUrl":"10.1007/s00109-025-02532-1","url":null,"abstract":"<p><p>Hepatoma is the sixth most malignant tumor in the world and the second leading cause of cancer death. Among the types of hepatoma, hepatocellular carcinoma (HCC) is the most important pathological type. For patients with early-stage HCC, the curative treatment is tumor resection. However, early diagnosis and treatment of HCC are difficult; the disease progresses rapidly, and the prognosis is poor. Due to the current limited treatment options for advanced HCC, the identification of new targeted agents is critical for the development of novel approaches to HCC treatment. Histone deacetylases (HDACs) is a protease that removes acetyl groups from histone lysine residues in proteins, and it plays an important role in the structural modification of chromosomes and the regulation of gene expression. Abnormally expressed HDACs can promote tumorigenesis by inducing biological processes such as cell proliferation, migration, and apoptosis inhibition. Since HDACs activity is upregulated in HCC, treatment regimens specifically inhibiting various HDACs have shown good efficacy. This article reviews the application of HDAC inhibitors in the treatment of HCC and explains their mechanisms of action. KEY MESSAGES: HDAC network and cellular effects of HDAC inhibitors. Role and mechanism of HDAC inhibitors in HCC. HDAC inhibitor combined with other ways to treat HCC. The side effects of HDACis in the treatment of HCC.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"469-484"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711969","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":"Lipidomic insights on abdominal aortic aneurysm and peripheral arterial disease.","authors":"Helena Beatriz Ferreira, Fábio Trindade, Rita Nogueira-Ferreira, Adelino Leite-Moreira, Rita Ferreira, Marina Dias-Neto, M Rosário Domingues","doi":"10.1007/s00109-025-02524-1","DOIUrl":"10.1007/s00109-025-02524-1","url":null,"abstract":"<p><p>Abdominal aortic aneurysm (AAA) and peripheral arterial disease (PAD) are two cardiovascular diseases associated with considerable morbidity, mortality and quality of life impairment. As they are multifactorial diseases, several factors contribute to their pathogenesis, including oxidative stress and lipid peroxidation, and these may have key roles in the development of these pathologies. Alterations of the lipid metabolism and lipid profile have been reported in cardiovascular diseases but to a lesser extent in AAA and PAD. Modifications in the profile of some molecular lipid species, in particular, native phospholipid and triglyceride species were mainly reported for AAA, while alterations in the fatty acid profile were noticed in the case of PAD. Oxidized phospholipids were also reported for AAA. Although AAA and PAD have a common atherosclerotic root, lipidomics demonstrates the existence of distinct lipid. Lipidomic research regarding AAA and PAD is still scarce and should be set in motion to increase the knowledge on the lipid changes that occur in these diseases, contributing not only to the discovery of new biomarkers for diagnosis and prognosis assessment but also to tailor precision medicine in the clinical field.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"365-380"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517040","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":"Regulatory role of annexin A1 in NLRP3 inflammasome activation in atopic dermatitis: insights from keratinocytes in human and murine studies.","authors":"Rebeca D Correia-Silva, Mab P Corrêa, Maria Eduarda de Castro, Joaquim S Almeida, Solange C G P D'Ávila, Sonia M Oliani, Karin V Greco, Cristiane D Gil","doi":"10.1007/s00109-025-02529-w","DOIUrl":"10.1007/s00109-025-02529-w","url":null,"abstract":"<p><p>Despite the well-documented regulatory role of annexin A1 (ANXA1) in numerous stages of the inflammatory response, its involvement in regulating the NLRP3 inflammasome in the context of allergic responses has not been extensively investigated to date. This study evaluated the expression patterns of the ANXA1 and NLRP3 proteins in human skin samples obtained from patients with atopic dermatitis (AD) and in mice with ovalbumin (OVA)-induced experimental AD. Furthermore, the in vitro effect of the ANXA1 mimetic peptide Ac2-26 on IL-4-stimulated human keratinocytes was evaluated. IL-4-stimulated keratinocytes were treated with Ac2-26 (a mimetic peptide of ANXA1) in two different concentrations: 5 and 25 ng/mL. Additionally, some cells were treated with the pan-formyl peptide receptor antagonist Boc2 at a concentration of 10 µM, administered 15 min before Ac2-26. The NLRP3 protein demonstrated intense immunoreactivity in both murine and human AD skin samples, with NLRP3 and ANXA1 exhibiting particularly high coexpression in keratinocytes. A significant increase in ANXA1 and NLRP3 transcripts was observed in AD skins (GSE16161 study). ANXA1 transcript levels were elevated in the AD epidermis relative to the non-lesional epidermis, while NLRP3 transcript levels were reduced in the AD epidermis (GSE120721 study). The Ac2-26 treatment reduced the proliferation rate of IL-4-stimulated keratinocytes, an effect abolished by Boc2 and IL-1β and ROS production. In conclusion, our findings indicate that ANXA1 plays a role in regulating NLRP3 activation in keratinocytes, contributing to the pathogenesis of AD. KEY MESSAGES: ANXA1 and NLRP3 levels are upregulated and exhibit coexpression in murine and human AD skins. ANXA1-FPR axis regulates the proliferation of human keratinocytes under IL-4 stimulation. ANXA1-derived peptide Ac_2-26 regulates oxidative stress and NLRP3 activation in human keratinocytes.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"435-451"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659055","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":"Correction to: Metanephric mesenchyme-derived Foxd1⁺ mesangial precursor cells alleviate mesangial proliferative glomerulonephritis.","authors":"Meiling Jin, Zhong Yin, Kai Wei, Yuansheng Xie, Xueyuan Bai, Bo Fu, Zhe Feng, Qinggang Li, Xiangmei Chen","doi":"10.1007/s00109-025-02526-z","DOIUrl":"10.1007/s00109-025-02526-z","url":null,"abstract":"","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"485-487"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568764","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":"Macrophage co-culture promotes cell reprogramming and prevents ferroptosis in aging fibroblasts for neurodegeneration therapy.","authors":"Lunjie Ma, Fei Fang, Haonan Wang, Ping Zhao, Hongchi Yu, Xiaoheng Liu","doi":"10.1007/s00109-025-02518-z","DOIUrl":"10.1007/s00109-025-02518-z","url":null,"abstract":"<p><p>Ferroptosis, a form of programmed cell death associated with lipid peroxidation and iron dependency, plays a critical role in affecting neuronal function in the aging-related neurodegenerative diseases. Macrophages, influenced by these changes, contribute significantly to the progression of aging nerve diseases. Induced neuronal reprogramming is an advanced technology, which can direct convert somatic cells, such as fibroblasts, into neurons, and offers a promising approach for drug screening aimed at correcting ferroptosis and combating aging-related nerve diseases. However, the efficiency of this reprogramming process remains a significant challenge. In this study, we aimed to manipulate macrophage phenotypes to enhance the direct conversion of fibroblasts into neurons. Specifically, we sought to correct ferroptosis through screening natural compounds using aged fibroblasts and utilizing macrophages to promote induced neuronal (iN) reprogramming. Our findings demonstrate that M2 macrophages effectively promote the direct reprogramming of fibroblasts into iNs. In a novel macrophage-fibroblast co-culture system, M2 macrophages facilitate iN reprogramming by reducing fibroblast adhesion forces and promoting asymmetric cell division. Furthermore, we discovered that manipulating matrix stiffness can induce polarization of macrophages towards the M2 phenotype, thereby enhancing fibroblast reprogramming into iNs. To facilitate these findings, we developed a mechano-cue-based drug screening chip, where soft hydrogels induced and maintained the phenotype of M2 macrophages and effectively promoted cell reprogramming. Using a combinatorial approach with 36 such chips, we screened natural compounds for their anti-aging properties, focusing on reversing fibroblast aging and inducing their conversion into neuronal cells. Notably, Vitexin, an apigenin flavone glycoside with a role as a platelet aggregation inhibitor, emerged as a promising candidate to achieve our therapeutic goals. This study highlights the potential of macrophage-mediated modulation of fibroblast reprogramming as a strategy to address ferroptosis-induced neuronal dysfunction in aging-related nerve diseases. KEY MESSAGE: This study highlights the potential of macrophage-mediated modulation of fibroblast reprogramming as a strategy to address ferroptosis-induced neuronal dysfunction in aging-related nerve diseases.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"301-310"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076208","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":"Role of CYLD in brain physiology and pathology.","authors":"Leonardo Nardi, Frank Bicker, Jannik Maier, Ari Waisman, Michael J Schmeisser","doi":"10.1007/s00109-025-02521-4","DOIUrl":"10.1007/s00109-025-02521-4","url":null,"abstract":"<p><p>A common hallmark of several neuropsychiatric conditions is an altered protein homeostasis. In this context, ubiquitination has emerged as one of the most important post-translational modifications, regulating various intracellular processes such as protein degradation, autophagy, protein activation, and protein-protein interactions. Ubiquitination can be reversed by the activity of several deubiquitinating enzymes (DUBs), and it is of utmost importance that both processes remain in balance. Understanding the extent to which this system is involved in specific brain disorders opens up new possibilities for treating a broader spectrum of patients by targeting this central hub. In recent years, the attention to one of those DUBs, called CYLD, has increased sharply, but with relatively little focus on the central nervous system (CNS): 55 results for \"CYLD Brain\" vs. 895 results for \"CYLD\" in total (NCBI Pubmed search, 17.01.2025). Thus, we aim to provide a first overview of the new findings from the past decade specifically related to the role of CYLD in the physiology and pathology of the CNS.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"255-263"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411300","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":"Mediator kinase inhibition drives myometrial stem cell differentiation and the uterine fibroid phenotype through super-enhancer reprogramming.","authors":"Subash Khadka, Brandon Lukas, Claire Xin Sun, Sribalashubashini Muralimanoharan, Karthigayan Shanmugasundaram, Azad Khosh, Lindsey Barron, Claire Schenken, Nicholas Stansbury, Robert Schenken, Ron Firestein, Yang Dai, Thomas G Boyer","doi":"10.1007/s00109-025-02517-0","DOIUrl":"10.1007/s00109-025-02517-0","url":null,"abstract":"<p><p>Uterine fibroids (UFs) are the most common non-cutaneous tumors in women worldwide. UFs arise from genetic alterations in myometrial stem cells (MM SCs) that trigger their transformation into tumor-initiating cells (UF SCs). Mutations in the RNA polymerase II Mediator subunit MED12 are dominant drivers of UFs, accounting for 70% of these clinically significant lesions. Biochemically, UF driver mutations in MED12 disrupt CDK8/19 kinase activity in Mediator, but how Mediator kinase disruption triggers MM SC transformation remains unknown. Here, we show that pharmacologic inhibition of CDK8/19 in MM SCs removes a barrier to myogenic differentiation down an altered pathway characterized by molecular phenotypes characteristic of UFs, including oncogenic growth and extracellular matrix (ECM) production. These perturbations appear to be induced by transcriptomic changes, arising in part through epigenomic alteration and super-enhancer reprogramming, that broadly recapitulate those found in MED12-mutant UFs. Altogether, these findings provide new insights concerning the biological role of CDK8/19 in MM SC biology and UF formation. KEY MESSAGES: Mediator kinase inhibition in myometrial stem cells (MM SCs) induces spontaneous differentiation. Transcriptional changes upon Mediator kinase inhibition recapitulate those of MED12 mutant uterine fibroids (UFs). Such transcriptional changes are partially mediated by super-enhancer reprogramming. Mediator kinase functions to enforce cell states and its loss induces cellular plasticity.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"311-326"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191349","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":"Hereditary non-spherocytic hemolytic anemia with GPI mutations successfully treated with allogeneic hematopoietic stem cell transplantation: a first report of two cases.","authors":"Huimin Li, Jiali Wang, Liucheng Rong, Jian Li, Yao Xue, Yongjun Fang, Yaping Wang","doi":"10.1007/s00109-025-02514-3","DOIUrl":"10.1007/s00109-025-02514-3","url":null,"abstract":"<p><p>Glucose phosphate isomerase (GPI) deficiency caused by GPI gene mutations is a rare heterogenous condition that causes hereditary non-spherocytic hemolytic anemia (HNSHA). Patients who suffer from severe anemia may need more effective treatment. Here, clinical data and genetic testing results of two cases of HNSHA with GPI mutations treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) were retrospectively analyzed. Specifically, two unrelated 6-year-old male patients with severe hemolytic anemia had hemoglobin (Hb) below the normal range despite frequent blood transfusions. Two novel missense mutations in the GPI gene were detected in them, respectively. They underwent peripheral blood stem cell (PBSC) transplantation successfully, and there was no anemia post-transplantation. In conclusion, HNSHA caused by mutations of the GPI gene is inherited in an autosomal recessive (AR) manner. Allo-HSCT offers an acceptable therapeutic efficacy and improvement of quality of life in HNSHA patients with GPI mutations. Our study expands the genetic spectrum of GPI deficiency. KEY MESSAGES: We reported for the first time that two cases of hereditary non-spherocytic hemolytic anemia with GPI mutations successfully treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Two novel missense mutations in GPI gene were detected in each of the two cases, respectively, which were predicted to be pathogenic or damaging. Our study expands the genetic spectrum of GPI deficiency. Allo-HSCT offers an acceptable therapeutic efficacy and improvement of quality of life in HNSHA patients with GPI mutations.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"265-271"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015333","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":"Glucose enrichment reduces lifespan and promotes tau phosphorylation in human tau-expressing C. elegans, unaffected by O-β-GlcNAcylation induction.","authors":"Waqar Ahmad, Khadija Shabbiri","doi":"10.1007/s00109-025-02522-3","DOIUrl":"10.1007/s00109-025-02522-3","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is associated with the formation of tau-hyperphosphorylated neurofibrillary tangles (NFTs). Impaired glucose metabolism has been proposed as a major risk factor in AD severity, with many enzymes and pathways associated with glucose metabolism found to be compromised. The use of additional glucose has been suggested to reduce AD severity. However, the exact role of glucose metabolism in disease progression is still under investigation. In this study, we found that adding glucose to tau-expressing worms not only shortens their lifespan but also induces tau phosphorylation on critical serine and threonine residues. Increased phosphorylation of tau is associated with the formation of NFTs and increased disease severity. O-β-GlcNAcylation may inhibit phosphorylation. We hypothesized that high glucose levels might induce tau O-β-GlcNAcylation, thereby protecting against tau phosphorylation. Contrary to our expectations, glucose increased tau phosphorylation but not O-β-GlcNAcylation. Increasing O-β-GlcNAcylation, either with Thiamet-G (TMG) or by suppressing the O-GlcNAcase (oga-1) gene, interferes with and reduces tau phosphorylation. Conversely, reducing O-β-GlcNAcylation by suppressing the O-GlcNAc transferase (ogt-1) gene increases tau phosphorylation. Our results suggest that glucose addition may induce selective O-β-GlcNAcylation on some proteins but not on tau. High levels of glucose exacerbate disease progression by promoting tau hyperphosphorylation. The effects of glucose cannot be effectively managed by manipulating O-β-GlcNAcylation in tau models of AD in C. elegans. Our observations indicate that glucose enrichment is unlikely to be an appropriate therapy to minimize AD progression. KEY MESSAGES: Formation of tau hyperphosphorylated neurofibrillary tangles are hallmarks of Alzheimer's disease (AD) in aged patients. Glucose metabolism may affect the AD pathogenesis. Glucose was found to induce tau phosphorylation. Glucose intake was not able to induce overall O-β-GlcNAcylation. Collectively, higher glucose levels in diet were associated with induced disease severity.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"327-338"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383936","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":"Kat7 accelerates osteoarthritis disease progression through the TLR4/NF-κB signaling pathway.","authors":"Zhen Liu, Lijie Qiu, Yongqiang Zhang, Gang Zhao, Xuecheng Sun, Wenming Luo","doi":"10.1007/s00109-025-02519-y","DOIUrl":"10.1007/s00109-025-02519-y","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a common degenerative bone and joint disease with an unclear pathogenesis. Our study identified that the histone acetyltransferase encoded by Kat7 is upregulated in the affected articular cartilage of OA patients and in a mice model of medial meniscal instability-induced OA. Chondrocyte-specific knockdown of Kat7 expression exhibited a protective effect on articular cartilage integrity. In vitro experiments demonstrated that KAT7 promotes cartilage catabolism, inhibits cartilage anabolism, and induces chondrocyte senescence and apoptosis. Conversely, knocking down Kat7 was shown to protect chondrocyte function. Corresponding in vivo results indicated that silencing Kat7 effectively enhances cartilage anabolism, prevents articular cartilage damage, and significantly slows OA progression. Mechanistically, KAT7 activates the TLR4/NF-κB signaling pathway, and inhibition of this pathway reverses the catabolic effects and restores anabolic activity in the presence of Kat7 overexpression. Collectively, these findings confirm the critical role of KAT7 in the pathogenesis of OA and suggest that Kat7 represents a potential therapeutic target for OA treatment. KEY MESSAGES: There is a lack of clinically effective drugs for the treatment of osteoarthritis (OA). Kat7 plays a key role in the development of OA. Knocking down Kat7 expression can alleviate the progression of OA. Kat7 accelerates the progression of OA by activating the TLR4/NF-KB signaling pathway.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"273-284"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054045","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}