Tuberculosis最新文献

{"title":"METTL3 contributes to M.tb-induced injury and inflammation in THP-1 macrophages by mediating m6A methylation of IRF8 to activate TLR4/NF-kB pathway","authors":"Yunhua Chen ,&nbsp;Xiaolin Tang ,&nbsp;Chao He ,&nbsp;Chong Xiao ,&nbsp;Ziping Zhao","doi":"10.1016/j.tube.2025.102667","DOIUrl":"10.1016/j.tube.2025.102667","url":null,"abstract":"<div><h3>Background</h3><div>Macrophages play central roles in the immunity response to infection of intracellular bacteria, including <em>Mycobacterium tuberculosis</em> (M.tb) in tuberculosis (TB). Methyltransferase-like 3 (METTL3) has been implicated in the macrophage regulation in TB, and this study intended to investigate the molecular mechanism of METTL3 with interferon regulatory factor-8 (IRF8) in TB using <em>in vitro</em> model established by M.tb-infected THP-1 macrophages.</div></div><div><h3>Methods</h3><div>RT-qPCR and Western blot were utilized to analyze mRNA and protein expression, respectively. Cell viability, proliferation, and apoptosis were examined through cell counting kit-8 assay, EdU assay, and flow cytometry/TUNEL assay. Inflammatory cytokines were detected via enzyme-linked immunosorbent assay. Methylated RNA Immunoprecipitation (MeRIP), RIP and Co-IP were performed to assess the interaction between genes.</div></div><div><h3>Results</h3><div>IRF8 knockdown alleviated injury and inflammation in M.tb-infected THP-1 macrophages. METTL3 enhanced IRF8 mRNA stability by inducing m⁶A methylation. IGF2BP1 functioned as an m⁶A reader to affect m⁶A methylation of IRF8. The function of METTL3 in M.tb-induced THP-1 macrophages was attributed to the positive regulation of IRF8. IRF8 bound to TLR4 and METTL3 could regulate TLR4 expression via targeting IRF8. IRF8/TLR4 axis promoted M.tb-induced THP-1 cell injury and inflammation. TLR4/NF-kB pathway was activated by METTL3-mediated IRF8.</div></div><div><h3>Conclusion</h3><div>These findings revealed that METTL3 expedited cell injury and inflammatory reaction in M.tb-infected THP-1 macrophages by inducing m⁶A methylation of IRF8 to activate TLR4/NF-kB pathway.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102667"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511093","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":"Exploring novel salivary host biomarkers for immunological diagnosis of tuberculosis: A preliminary biomarker discovery study","authors":"Pavithra Selvan ,&nbsp;Nalini Jayanthi Nagesh ,&nbsp;Leela Kakithakara Vajravelu","doi":"10.1016/j.tube.2025.102669","DOIUrl":"10.1016/j.tube.2025.102669","url":null,"abstract":"<div><div>Tuberculosis is a serious public health concern on a global scale, which emphasises the critical need for quick and precise diagnostic and treatment response monitoring techniques. In this study, Luminex multiplex immunoassay was used to detect the concentrations of 37 host biomarkers in saliva samples from 46 patients newly diagnosed with active pulmonary tuberculosis (PTB) and 46 patients with other respiratory diseases (ORD). Multiple logistic regression and the area under the receiver operator characteristics curve (AUC) were used to evaluate the diagnostic accuracy of biomarkers, which showed significant differences between the 2 groups. This study reported that Fractalkine exhibited the highest diagnostic accuracy and excellent discriminatory power, with statistically significant results (p ≤ 0.05), an AUC of 0.91, 89.1 % sensitivity and 76.1 % specificity, highlighting its strong potential to distinguish PTB cases from ORD cases. Additionally, our study found that the median levels of IL-17A, IL-23, and VEGF were statistically significant (p ≤ 0.05). General discriminant analysis further identified Fractalkine, VEGF, GM-CSF, IL-23, and IL-1α as the top five most effective biomarkers for combinations. The backward elimination approach demonstrated the potential usefulness of a four-marker combination (Fractalkine + GM-CSF + IL-23 + IL-1α) as a confirmatory diagnostic tool by achieving the greatest overall diagnostic accuracy with an AUC of 0.94 and 91.3 % specificity. Thus, combining multiple markers with high discriminating power may improve diagnostic performance and subsequently provide a more accurate, non-invasive saliva-based PTB diagnostic tool.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102669"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563629","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":"Correspondence on “Analysis of the cross-study replicability of tuberculosis gene signatures using 49 curated human transcriptomic datasets”","authors":"Hinpetch Daungsupawong ,&nbsp;Viroj Wiwanitkit","doi":"10.1016/j.tube.2025.102677","DOIUrl":"10.1016/j.tube.2025.102677","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102677"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800389","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":"Biomarkers for diagnosing pulmonary tuberculosis in adolescents: Peripheral blood monocyte myotubularin-related protein 4 and oncostatin M genes","authors":"Yuxia Sha ,&nbsp;Haoquan Zhou ,&nbsp;Bingda Yan ,&nbsp;Xianzong Da ,&nbsp;Meilin Shao ,&nbsp;Ye Li ,&nbsp;Shenggang Ding","doi":"10.1016/j.tube.2025.102676","DOIUrl":"10.1016/j.tube.2025.102676","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background/objectives&lt;/h3&gt;&lt;div&gt;Although research has increasingly been focused on pulmonary tuberculosis (PTB) in adolescents, its diagnosis remains complex and challenging. Thus, the use of host transcription markers in the diagnosis of adolescent PTB was evaluated in this study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The study cohort comprised 40 adolescents (aged 14–18 years) with PTB who had received their first PTB diagnosis at Anhui Provincial Chest Hospital, China, between January and December 2023 (case group) and 32 healthy adolescents who had undergone physical examinations at The First Affiliated Hospital of the University of Science and Technology of China during the same period (control group). Peripheral blood samples were collected from both groups, and isolated monocytes were subjected to transcriptome sequencing and bioinformatic analysis. The relevant genes were confirmed through quantitative polymerase chain reaction. The diagnostic value of these genes in adolescent PTB patients was analysed using receiver operating characteristic curves. Furthermore, an in vitro model was constructed by infecting THP-1 cells with the &lt;em&gt;Mycobacterium tuberculosis&lt;/em&gt; strain H37Ra to assess whether the in vitro expression levels of the identified genes were consistent with those of the genes in the peripheral blood monocytes of adolescents with PTB. The specific mechanisms were explored using methods such as lentiviral infection, flow cytometry, immunofluorescence, Western blotting, and qRT‒PCR.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The results revealed that the expression level of the &lt;em&gt;myotubularin-related protein 4&lt;/em&gt; gene (&lt;em&gt;MTMR4&lt;/em&gt;) was lower in the case group than in the control group (&lt;em&gt;P&lt;/em&gt; &lt; 0.0001; area under the curve: 0.946; 95 % confidence interval: 0.893–0.999; cut-off value: 0.844; sensitivity: 0.875; specificity: 0.969). The expression level of the &lt;em&gt;oncostatin M&lt;/em&gt; gene (&lt;em&gt;OSM&lt;/em&gt;) was greater in the case group than in the control group (&lt;em&gt;P&lt;/em&gt; = 0.014; area under the curve: 0.962; 95 % confidence interval: 0.914–1.000; cut-off value: 0.919; sensitivity: 0.950; specificity: 0.969). However, no significant between-group difference was detected in the expression level of the complement &lt;em&gt;component 1q subcomponent A&lt;/em&gt; gene. The results from the in vitro experiment indicated that the expression levels of &lt;em&gt;MTMR4&lt;/em&gt; and &lt;em&gt;OSM&lt;/em&gt; were consistent between the H37Ra-infected cells and the case group samples. Bioinformatics analysis revealed that cytokine–cytokine receptor interactions, JAK/STAT signalling and PI3K/cell survival-related pathways play key roles in the pathogenesis of adolescent PTB. Additionally, we found that H37Ra infection affected tuberculosis progression via the OSM/PI3K/GPX4 pathway.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Peripheral blood monocyte &lt;em&gt;OSM&lt;/em&gt; and &lt;em&gt;MTMR4&lt;/em&gt; may serve as biomarkers of adolescent PTB. We speculate that targeting the OSM signallin","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102676"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144809517","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":"MicroRNAs in exhaled breath Condensate: Novel non-invasive biomarkers for tuberculosis diagnosis","authors":"Tak Jaya ,&nbsp;Pattnaik Bijay ,&nbsp;Rai Divyanjali ,&nbsp;Bhatraju Naveen ,&nbsp;P.P. Adwika ,&nbsp;Bangaru Sunil ,&nbsp;Sunita Yadav ,&nbsp;Sachin kumar ,&nbsp;Seetu Kumari ,&nbsp;Umashankar Verma ,&nbsp;Geetika Yadav ,&nbsp;R.S. Dhaliwal ,&nbsp;Saurabh Mittal ,&nbsp;Pawan Tiwari ,&nbsp;Vijay Hadda ,&nbsp;Karan Madan ,&nbsp;Anurag Agrawal ,&nbsp;Randeep Guleria ,&nbsp;Tapasya Srivastava ,&nbsp;Anant Mohan","doi":"10.1016/j.tube.2025.102670","DOIUrl":"10.1016/j.tube.2025.102670","url":null,"abstract":"<div><h3>Background</h3><div>Tuberculosis remains a significant global health issue. Sputum smear microscopy has low sensitivity, making it difficult to diagnose. Analysis of miRNA from EBC (exhaled breath condensate) offers a potential non-invasive diagnostic method that could improve sensitivity and specificity for TB detection, including extrapulmonary TB (EPTB).</div></div><div><h3>Method</h3><div>EBC was collected from 65 treatment naïve TB patients and 65 healthy controls. miRNA profiling was done on an exploratory set (n = 40) using the qRT-PCR-based miRNome profiler kit, and shortlisted miRNAs were validated in a separate set (n = 25) using qRT-PCR. ROC curves were used to evaluate diagnostic performance.</div></div><div><h3>Result</h3><div>In this study, we identified eight differentially expressed miRNAs in TB vs healthy subjects (seven upregulated, one downregulated). Comparing PTB with EPTB, five miRNAs were upregulated and 68 miRNAs were downregulated in PTB. Between PTB and healthy controls, six miRNAs were upregulated and 16 miRNAs were downregulated in PTB, while in EPTB, 132 miRNAs were upregulated compared with controls. Validation confirmed upregulation of miR-454, miR-139, and miR-143 in tuberculosis.</div></div><div><h3>Conclusion</h3><div>The findings of our study indicate that the expression of miR-143, miR-454, and miR-139 in exhaled breath condensate has strong potential as a non-invasive biomarker for TB diagnosis.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102670"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663396","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":"In vitro and in vivo activities of a novel benzothiopyranone candidate NTB-3119M against Mycobacterium tuberculosis","authors":"Manyi Xu ,&nbsp;Lei Zhang ,&nbsp;Bin Wang ,&nbsp;Lei Fu ,&nbsp;Shaochen Guo ,&nbsp;Xi Chen ,&nbsp;Weiyan Zhang ,&nbsp;Gang Li ,&nbsp;Peng Li ,&nbsp;Haihong Huang ,&nbsp;Yu Lu","doi":"10.1016/j.tube.2025.102654","DOIUrl":"10.1016/j.tube.2025.102654","url":null,"abstract":"<div><h3>Objectives</h3><div>NTB-3119M, a novel benzothiopyranone derivative identified through comprehensive drug development studies, was selected as a promising antituberculosis (anti-TB) candidate. This study systematically evaluated its anti-TB efficacy <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Methods</h3><div><em>In vitro</em> analyses encompassed antimicrobial susceptibility testing to determine minimum inhibitory concentrations (MICs) against <em>Mycobacterium tuberculosis</em> H37Rv, 10 drug-susceptible clinical isolates, and 30 multidrug-resistant (MDR) strains, alongside evaluations of minimal bactericidal concentrations (MBCs) using H37Rv and seven clinical isolates. Additionally, intracellular anti-mycobacterial activity was assessed in H37Rv-infected macrophages, and cytotoxicity was profiled through MTT assays on Vero cells. <em>In vivo</em> studies utilized acute and chronic murine tuberculosis infection models to investigate the dose-dependent efficacy of NTB-3119M (50 and 100 mg/kg) against H37Rv, with concurrent comparative histopathological analysis of lung and spleen tissues.</div></div><div><h3>Results</h3><div>NTB-3119M demonstrated superior <em>in vitro</em> potency against both drug-sensitive and drug-resistant <em>M. tuberculosis</em> strains compared to first-line agents, Isoniazid (INH), Rifampicin (RIF), Moxifloxacin (MOFX), Levofloxacin (LVFX), and Streptomycin (SM), exhibiting comparable activity to PBTZ169. Time-kill curves for NTB-3119M indicate its potent bactericidal activity. Meanwhile, No cytotoxicity was observed on Vero cells. Spontaneous resistant mutants of NTB-3119M appears at a frequency of 6.44 × 10⁻⁷ to 3.65 × 10⁻⁶. Most importantly, NTB-3119M demonstrates comparable activity of PBTZ169 and better bactericidal activity against <em>M. tuberculosis</em> than INH and RIF in the 50- and 100- mg/kg groups in acute and chronic murine models.</div></div><div><h3>Conclusion</h3><div>Our research provided comprehensive evidence that NTB-3119M with increased water solubility and bioavailability based on previous research performed excellent anti-tuberculosis activity and less cytotoxicity, which effectively tackled the undesirable drug properties associated with previous benzothiopyrone derivatives. It is warranted that NTB-3119M, as a highly promising candidate anti tuberculosis drug, deserves further research and clinical trial.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102654"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230347","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":"CRISPRi-mediated repression of efflux pumps reveals Rv1258c as a key contributor to pyrazinamide resistance in Mycobacterium tuberculosis","authors":"Carlos Alonso Flores B. ,&nbsp;Kiara Aricoche-Del Campo ,&nbsp;Robert H. Gilman ,&nbsp;Mirko Zimic ,&nbsp;Patricia Sheen","doi":"10.1016/j.tube.2025.102665","DOIUrl":"10.1016/j.tube.2025.102665","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102665"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471757","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":"Response to “Correspondence on ‘Analysis of the cross-study replicability of tuberculosis gene signatures using 49 curated human transcriptomic datasets’”","authors":"Xutao Wang ,&nbsp;Katie Harper ,&nbsp;Pranay Sinha ,&nbsp;W. Evan Johnson ,&nbsp;Prasad Patil","doi":"10.1016/j.tube.2025.102678","DOIUrl":"10.1016/j.tube.2025.102678","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102678"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859669","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":"In vitro and in vivo antibacterial activity of sudapyridine (WX-081) combined with other drugs against Mycobacterium abscessus","authors":"Hong Wang ,&nbsp;Luyao Zheng ,&nbsp;Lei Fu ,&nbsp;Weiyan Zhang ,&nbsp;Shaoyu Dong ,&nbsp;Xiaoyou Chen ,&nbsp;Yu Lu","doi":"10.1016/j.tube.2025.102655","DOIUrl":"10.1016/j.tube.2025.102655","url":null,"abstract":"<div><div>The management of <em>Mycobacterium abscessus</em> (MAB) infection presents formidable challenges, necessitating the development of innovative antimicrobial agents and more efficacious combination therapies. The objective of this study was to investigate the <em>in vitro</em>, <em>intracellular</em>, and <em>in vivo</em> antibacterial activity of sudapyridine (WX-081) in combination with clarithromycin (CLR), clofazimine (CFZ), rifabutin (RFB), and linezolid (LZD) against MAB. <em>In vitro</em>, the interaction between WX-081 and other drugs was assessed using the checkerboard method against MAB. Synergistic or additive effects were observed when combining WX-081 with other drugs against all strains tested. The intracellular activity of WX-081 in combination with CLR, CFZ, RFB, and LZD against the MAB reference strain in J774A.1 cells was evaluated. The combination of WX-081 and CFZ or RFB exhibited potent inhibitory activity against MAB in macrophages. To evaluate pharmacodynamics, immunosuppressed BALB/c mice were infected with MAB to establish a murine model for assessing two-drug and three-drug combinations. <em>In vivo</em> studies demonstrated that the combination of WX-081 with CLR or both CLR and CFZ displayed antibacterial activity and significantly prevented mouse mortality. Our study demonstrates that the concurrent use of WX-081 with CLR or CLR plus CFZ holds significant promise as a clinical intervention for MAB infection.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102655"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230356","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":"Hereditary and antimicrobial factor shaping extracellular bacteria dynamics in an in-host mathematical model of tuberculosis for disease control","authors":"Morufu Oyedunsi Olayiwola ,&nbsp;Ezekiel Abiodun Oluwafemi","doi":"10.1016/j.tube.2025.102668","DOIUrl":"10.1016/j.tube.2025.102668","url":null,"abstract":"<div><div>Tuberculosis (TB) remains a global health challenge, necessitating deeper insights into the dynamics of extracellular bacterial populations within infected hosts. This study presents an in-host mathematical model that incorporates hereditary and antimicrobial factors influencing TB progression. The biological feasibility of the model is established by analyzing the boundedness of solutions within a realistic parameter space. The equilibrium states, including the disease-free and endemic equilibria, are examined, revealing conditions under which the system remains locally asymptotically stable. Sensitivity analysis is conducted to determine the key parameters driving infection dynamics, providing insights into potential control strategies. Notably, the model exhibits a backward bifurcation, indicating the possibility of multiple stable states and suggesting that reducing the basic reproduction number R₀ below unity may not be sufficient for disease eradication. These findings highlight the importance of targeted interventions to effectively control extracellular bacterial populations and mitigate TB infection.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102668"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556722","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}