Tuberculosis最新文献

{"title":"Isoniazid exposures and acetylator status in Indonesian tuberculous meningitis patients","authors":"Vycke Yunivita ,&nbsp;Lindsey te Brake ,&nbsp;Sofiati Dian ,&nbsp;Ahmad Rizal Ganiem ,&nbsp;Reinout van Crevel ,&nbsp;Rovina Ruslami ,&nbsp;Rob Aarnoutse","doi":"10.1016/j.tube.2023.102465","DOIUrl":"10.1016/j.tube.2023.102465","url":null,"abstract":"<div><p><span>The effect of acetylator status on the exposure to isoniazid in plasma and CSF in tuberculous meningitis (TBM) patients remains largely unexplored. Here, we describe isoniazid exposures and acetylator status of 48 subjects in the ReDEFINe study (NCT02169882). Fifty percentwere fast (half-life &lt;130 min) or slow (half-life &gt;130 min) acetylators. Slow acetylators had higher AUC</span>_0-24, C_max and CSF concentrations than fast acetylators (GM AUC_0-24 25.5 vs 10.6 mg/L*h, p &lt; 0.001); plasma C_max 5.5 vs 3.6 mg/L, p = 0.023; CSF concentration 1.9 vs 1.1 mg/L, p = 0.008). Higher isoniazid doses may benefit fast acetylators in TBM.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"144 ","pages":"Article 102465"},"PeriodicalIF":3.2,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138825647","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":"Antibody response to mycobacterial Rpf B protein and its immunodominant peptides in HIV-TB co-infected individuals","authors":"Madhur Kalyan ,&nbsp;Sumedha Sharma ,&nbsp;Prabhdeep Kaur ,&nbsp;Aman Sharma ,&nbsp;Indu Verma","doi":"10.1016/j.tube.2023.102464","DOIUrl":"10.1016/j.tube.2023.102464","url":null,"abstract":"<div><p><span>Diagnosis of TB at early stages of HIV infection may lead to timely intervention for improving patient outcome. Antibodies to </span><span><em>Mycobacterium tuberculosis</em></span> recombinant RpfB protein and two immunodominant peptides of Rpf B protein were evaluated in the sera of HIV ⁺TB⁺, HIV⁺ and HIV⁻<span> pulmonary TB patients by ELISA<span>. Serum antibodies from 90 % and 65 % of HIV</span></span>⁺TB⁺<span> patients reacted to recombinant RpfB protein and synthetic peptide<span> RpfP1 respectively. Overall, this study shows that resuscitation promoting factor B<span> elicits humoral antibody response in HIV</span></span></span>⁺TB⁺ co-infected individuals and be proposed as a potential biomarker for diagnosis of HIV⁺TB⁺ patients, however further longitudinal follow up studies are warranted.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"144 ","pages":"Article 102464"},"PeriodicalIF":3.2,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138716648","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":"mRNA profiling of cytokines to understand paradoxical response in HIV-uninfected tuberculous meningitis","authors":"Jayantee Kalita ,&nbsp;Ruchi Shukla ,&nbsp;Prakash C. Pandey ,&nbsp;Vivek Singh ,&nbsp;Rudrashish Haldar ,&nbsp;Usha K. Misra","doi":"10.1016/j.tube.2023.102463","DOIUrl":"10.1016/j.tube.2023.102463","url":null,"abstract":"<div><p><span><span><span>Paradoxical reaction (PR) in tuberculous meningitis (TBM) is a major management issue. We report mRNA profiling of cytokines to understand PR in HIV-uninfected TBM patients. 72 patients with TBM were included, and their clinical, MRI, and mRNA profiling of tumor necrosis factor (TNF) α, interleukin (IL) 6, IL10 and interferon (IFN) γ genes in the </span>peripheral blood mononuclear cells were done at admission and 6 weeks of antitubercular </span>treatment<span>. Cytokine profiling was done using reverse transcriptase polymerase chain reaction. PR was defined if repeat MRI at 6 weeks revealed new or increase in exudates, </span></span>tuberculoma<span>, hydrocephalus<span> or infarctions. Outcome was defined at 6 months using modified Rankin Scale (mRS), and categorized as death, poor and good. 44 (61.1 %) patients had PR, and 28 (38.9 %) had paradoxical tuberculoma (PT). The expression of IL6 and TNFα genes were higher in PR and PT groups. Stage of meningitis and hydrocephalus at admission predicted PR. Patients with PR and PT had more frequently poor outcome.</span></span></p><p>About three-fifth HIV-uninfected TBM patients have PR and two-fifth have PT. Paradoxical reaction is associated with higher expression of IL6 and TNFα. Patients with severe meningitis with hydrocephalus develop PR more frequently.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"144 ","pages":"Article 102463"},"PeriodicalIF":3.2,"publicationDate":"2023-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138562319","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":"Integrative and comparative genomic analyses of mammalian macrophage responses to intracellular mycobacterial pathogens","authors":"Thomas J. Hall ,&nbsp;Gillian P. McHugo ,&nbsp;Michael P. Mullen ,&nbsp;James A. Ward ,&nbsp;Kate E. Killick ,&nbsp;John A. Browne ,&nbsp;Stephen V. Gordon ,&nbsp;David E. MacHugh","doi":"10.1016/j.tube.2023.102453","DOIUrl":"10.1016/j.tube.2023.102453","url":null,"abstract":"<div><p><em>Mycobacterium tuberculosis</em>, the causative agent of human tuberculosis (hTB), is a close evolutionary relative of <em>Mycobacterium bovis</em>, which causes bovine tuberculosis (bTB), one of the most damaging infectious diseases to livestock agriculture. Previous studies have shown that the pathogenesis of bTB disease is comparable to hTB disease, and that the bovine and human alveolar macrophage (bAM and hAM, respectively) transcriptomes are extensively reprogrammed in response to infection with these intracellular mycobacterial pathogens. In this study, a multi-omics integrative approach was applied with functional genomics and GWAS data sets across the two primary hosts (<em>Bos taurus</em> and <em>Homo sapiens</em>) and both pathogens (<em>M. bovis</em> and <em>M. tuberculosis</em>). Four different experimental infection groups were used: 1) bAM infected with <em>M. bovis</em>, 2) bAM infected with <em>M. tuberculosis</em>, 3) hAM infected with <em>M. tuberculosis</em>, and 4) human monocyte-derived macrophages (hMDM) infected with <em>M. tuberculosis</em>. RNA-seq data from these experiments 24 h post-infection (24 hpi) was analysed using three computational pipelines: 1) differentially expressed genes, 2) differential gene expression interaction networks, and 3) combined pathway analysis. The results were integrated with high-resolution bovine and human GWAS data sets to detect novel quantitative trait loci (QTLs) for resistance to mycobacterial infection and resilience to disease. This revealed common and unique response macrophage pathways for both pathogens and identified 32 genes (12 bovine and 20 human) significantly enriched for SNPs associated with disease resistance, the majority of which encode key components of the NF-κB signalling pathway and that also drive formation of the granuloma.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"147 ","pages":"Article 102453"},"PeriodicalIF":3.2,"publicationDate":"2023-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979223001725/pdfft?md5=3b5a04194dcb985c4ae9253d4b8ab5e0&pid=1-s2.0-S1472979223001725-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138518446","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":"Combined cerebrospinal fluid metabolomic and cytokine profiling in tuberculosis meningitis reveals robust and prolonged changes in immunometabolic networks","authors":"Jeffrey Tomalka ,&nbsp;Ashish Sharma ,&nbsp;Alison G.C. Smith ,&nbsp;Teona Avaliani ,&nbsp;Mariam Gujabidze ,&nbsp;Tinatin Bakuradze ,&nbsp;Shorena Sabanadze ,&nbsp;Dean P. Jones ,&nbsp;Zaza Avaliani ,&nbsp;Maia Kipiani ,&nbsp;Russell R. Kempker ,&nbsp;Jeffrey M. Collins","doi":"10.1016/j.tube.2023.102462","DOIUrl":"10.1016/j.tube.2023.102462","url":null,"abstract":"<div><p><span><span><span><span>Much of the high mortality in tuberculosis meningitis (TBM) is attributable to excessive inflammation, making it imperative to identify targets for host-directed therapies that reduce pathologic inflammation and mortality. In this study, we investigate how cytokines and metabolites in the cerebral spinal fluid (CSF) associate with TBM at diagnosis and during TBM </span>treatment. At diagnosis, TBM patients (n = 17) demonstrate significant increases of cytokines and </span>chemokines<span> that promote inflammation and cell migration including IL-17A, IL-2, TNFα, IFNγ, and IL-1β versus asymptomatic controls without known central nervous system pathology (n = 20). Inflammatory immune signaling had a strong positive correlation with immunomodulatory metabolites including </span></span>kynurenine, lactic acid, and </span>carnitine<span><span><span> and strong negative correlations with tryptophan and </span>itaconate. Inflammatory immunometabolic networks were only partially reversed with two months of effective TBM treatment and remained significantly different compared to CSF from controls. Together, these data highlight a critical role for host metabolism in regulating the inflammatory response to TBM and indicate the timeline for restoration of immune </span>homeostasis in the CSF is prolonged.</span></p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"144 ","pages":"Article 102462"},"PeriodicalIF":3.2,"publicationDate":"2023-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138518432","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":"Proteome and immunogenicity differences in BCG Pasteur ATCC 35734 and its derivative, the vaccine candidate BCGΔBCG1419c during planktonic growth in 7H9 and Proskauer Beck media","authors":"Mario Alberto Flores-Valdez ,&nbsp;Jesús Bernardino Velázquez-Fernández ,&nbsp;César Pedroza-Roldán ,&nbsp;Michel de Jesús Aceves-Sánchez ,&nbsp;Abel Gutiérrez-Ortega ,&nbsp;Wendy López-Romero ,&nbsp;Jeannette Barba-León ,&nbsp;Jacobo Rodríguez-Campos","doi":"10.1016/j.tube.2023.102432","DOIUrl":"https://doi.org/10.1016/j.tube.2023.102432","url":null,"abstract":"<div><p>Bacillus Calmette–Guérin (BCG) remains as the only vaccine employed to prevent tuberculosis (TB) during childhood. Among factors likely contributing to the variable efficacy of BCG is the variation in its antigenic repertoire that may arise from <em>in vitro</em><span> growth conditions. Our vaccine candidate, BCGΔBCG1419c, improved protection against TB in mice<span><span> and guinea pigs with bacteria grown in either 7H9 OADC </span>Tween 80<span> and in Proskauer Beck Tween 80 media in independent studies. Here, we compared the proteomes of planktonic cultures of BCG and BCGΔBCG1419c, grown in both media. Further to this, we compared systemic immunogenicity </span></span></span><span><em>ex vivo</em></span> elicited by both types of BCG strains and cultures when used to vaccinate BALB/c mice. Both the parental strain BCG Pasteur ATCC 35734, and its isogenic mutant BCGΔBCG1419c, had several medium-dependent changes. Moreover, <em>ex vivo</em> immune responses to a multiantigenic (PPD) or a single antigenic (Ag85A) stimulus were also medium-dependent. Then, not only the presence or absence of the <em>BCG1419c</em> gene in our strains under study affected the proteome produced <em>in vitro</em> but also that this was affected by culture medium, potentially leading to changes in the capacity to induce <em>ex vivo</em> immune responses.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"144 ","pages":"Article 102432"},"PeriodicalIF":3.2,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138466730","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-vivo expressed mycobacterial transcripts as diagnostic targets for pulmonary tuberculosis","authors":"Sumedha Sharma ,&nbsp;Ashutosh N. Aggarwal ,&nbsp;Prabhdeep Kaur ,&nbsp;Rakesh Yadav ,&nbsp;Sunil Sethi ,&nbsp;Indu Verma","doi":"10.1016/j.tube.2023.102431","DOIUrl":"https://doi.org/10.1016/j.tube.2023.102431","url":null,"abstract":"<div><p><span>The nucleic acid amplification tests (NAATs) such as Xpert MTB/RIF have transformed the TB diagnostic field by significantly increasing the case detection. However, newer improved diagnostic assays are still needed to meet the WHO targets to end TB. Present study is based on a novel approach of utilizing the </span><em>in-vivo</em><span> expressed specific mycobacterial transcriptomic<span> biomarkers for the diagnosis of pulmonary tuberculosis (PTB). A total of 61 subjects were recruited including smear positive (smear+, n = 15), smear negative (smear-, n = 30) PTB patients and disease controls (n = 16). Transcripts of three mycobacterial genes </span></span><em>Rv0986, Rv0971c</em> and <em>Rv3121</em><span><span> were analyzed using real time PCR (qRT-PCR) in </span>sputum samples. qRT-PCR with </span><em>Rv0986</em>, <em>Rv0971c</em> and <em>Rv3121</em> identified smear + PTB patients with 100 %, 78.6 % and 86.7 % sensitivity respectively. In smear- PTB patients, both <em>Rv0986</em> and <em>Rv0971c</em> based qRT-PCR resulted in 63 %, sensitivity whereas <em>Rv3121</em> identified these patients with ∼40 % sensitivity only. The sensitivity of the assay for smear-patients increased to 85 % when combinatorial analysis of qRT-PCR data for all the three genes was used. Thus, in-vivo expressed mycobacterial transcripts have promising potential as biomarkers for PTB diagnosis.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"144 ","pages":"Article 102431"},"PeriodicalIF":3.2,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138467986","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":"The first probable case with tuberculous meningitis from the Hun period of the Carpathian Basin – How diagnostics development can contribute to increase knowledge and understanding of the spatio-temporal distribution of tuberculosis in the past","authors":"Olga Spekker ,&nbsp;Luca Kis ,&nbsp;Nikoletta Lukács ,&nbsp;Eszter Patyi ,&nbsp;Balázs Tihanyi","doi":"10.1016/j.tube.2023.102372","DOIUrl":"https://doi.org/10.1016/j.tube.2023.102372","url":null,"abstract":"<div><p><span>The aim of our paper is to demonstrate and discuss in detail the endocranial bony changes suggestive of tuberculous meningitis (TBM) that were recorded in an adult female's (</span><strong>SPF15</strong><span>) skeleton. The bone remains were uncovered from a solitary grave from the Hun period (5th-century-CE) archaeological site of Solt–Polya-fok (Bács-Kiskun county, Hungary). During the macromorphological examination of the very incomplete and poorly preserved skeleton of </span><strong>SPF15</strong>, the inner surface of the skull displayed abnormally pronounced digital impressions (APDIs) and granular impressions (GIs). Recently, it was confirmed that endocranial GIs can be considered as specific signs of TBM; and thus, they are sufficient enough on their own to make a definitive diagnosis of the disease in the palaeopathological practice. On the other hand, APDIs are not specific to TBM but can be tuberculous in origin; their concomitant presence with GIs in <strong>SPF15</strong> makes their tuberculous origin very likely. Based on the above, it seems that the adult female from the 5th-century-CE archaeological site of Solt–Polya-fok suffered from TBM. <strong>SPF15</strong> is the first reported probable case with tuberculosis (TB) from the Hun period of the present-day territory of Hungary, who gives us invaluable information about the spatio-temporal distribution of the disease in the past. Furthermore, it highlights the paramount importance of diagnostics development, especially the identification and refinement of diagnostic criteria, as without the application of APDIs and GIs, the diagnosis of TB could not have been established in <strong>SPF15</strong>.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"143 ","pages":"Article 102372"},"PeriodicalIF":3.2,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138438175","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":"Re-examination of the Subalyuk Neanderthal remains uncovers signs of probable TB infection (Subalyuk Cave, Hungary)","authors":"György Pálfi ,&nbsp;Erika Molnár ,&nbsp;Zsolt Bereczki ,&nbsp;Hélène Coqueugniot ,&nbsp;Olivier Dutour ,&nbsp;Anne-marie Tillier ,&nbsp;Wilfried Rosendahl ,&nbsp;Antal Sklánitz ,&nbsp;Zsolt Mester ,&nbsp;Mihály Gasparik ,&nbsp;Frank Maixner ,&nbsp;Albert Zink ,&nbsp;David E. Minnikin ,&nbsp;Ildikó Pap","doi":"10.1016/j.tube.2023.102419","DOIUrl":"https://doi.org/10.1016/j.tube.2023.102419","url":null,"abstract":"<div><p><span>In 1932, skeletal remains of two Neanderthal individuals, a young adult female and a 3–4–year-old child, were discovered in Subalyuk Cave in Northern Hungary [1,2]. Results of the anthropological examination were published some years after this important discovery. Methodological progress encouraged re-examination of the material during the last few years. Radiocarbon dating revealed a chronological age of 39,732–39,076 cal. BP for the adult female and 36,117–35,387 cal. BP for the child [3]. Morphological paleopathological studies of these Neanderthal remains uncovered distinct evidence of skeletal infections. Alterations of the adult individual's </span><span><em>sacrum</em></span> suggest probable early-stage <span><em>sacroiliitis</em></span><span>, while several vertebral bodies indicate superficial osseous remodelling of infectious origin. Traces of pathological lesions were observed on the endocranial surface of the child's skull, reflecting a reaction of meningeal tissues, a consequence of a probable TB-related meningeal infectious process. Results of recent paleomicrobiological examinations – lipid biomarker and aDNA studies – support the morphological diagnosis of probable TB infections [4].</span></p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"143 ","pages":"Article 102419"},"PeriodicalIF":3.2,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138437699","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":"Professor David Minnikin Memorial Lecture: An era of the mycobacterial cell wall lipid biomarkers","authors":"Oona Y-C Lee ,&nbsp;Houdini H.T. Wu ,&nbsp;Gurdyal S. Besra","doi":"10.1016/j.tube.2023.102415","DOIUrl":"https://doi.org/10.1016/j.tube.2023.102415","url":null,"abstract":"<div><p>This paper is dedicated to the memory of Professor David Ernest Minnikin (1939–2021). David was one of the key scientists who pioneered the field of <em>Mycobacterium tuberculosis</em> cell envelope research for over half a century. From the classification, identification, and extraction of the unusual lipids of the mycobacterial cell wall, to exploiting them as characteristic lipid biomarkers for sensitive detection, his ideas enlightened a whole world of possibilities within the tuberculosis (TB) field. In addition, his definition of the intricate models now forms a key milestone in our understanding of the <em>M</em>. <em>tuberculosis</em> cell envelope and has resolved many unanswered questions on the evolution of <em>M. tuberculosis</em>.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"143 ","pages":"Article 102415"},"PeriodicalIF":3.2,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979223001130/pdfft?md5=8477bf506bcb078239d8a0633f6931fb&pid=1-s2.0-S1472979223001130-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138437782","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}