Hanna Marti, Kensuke Shima, Sebastien Boutin, Jan Rupp, Ian Clarke, Karine Laroucau, Nicole Borel
{"title":"Zoonotic and other veterinary chlamydiae - an update, the role of the plasmid and plasmid-mediated transformation.","authors":"Hanna Marti, Kensuke Shima, Sebastien Boutin, Jan Rupp, Ian Clarke, Karine Laroucau, Nicole Borel","doi":"10.1093/femspd/ftae030","DOIUrl":"https://doi.org/10.1093/femspd/ftae030","url":null,"abstract":"<p><p>The obligate intracellular bacterial genus Chlamydia harbours species with zoonotic potential, particularly C. psittaci, causative agent of psittacosis, and C. abortus, which may lead to miscarriage in pregnant women. The impact of other bird chlamydiae such as C. avium, C. gallinaceae and C. buteonis, or reptilian species such as C. crocodili, amongst others, on human health is unclear. The chlamydial native plasmid, a suspected virulence factor, is present in all currently described 14 Chlamydia species except for some plasmid-free strains. The plasmid is also the primary tool to study chlamydial genetics, a still developing field that has mostly focused on C. trachomatis. Only recently, genetic transformation of C. felis, C. pecorum, C. pneumoniae, C. psittaci and C. suis has succeeded, but existing methods have yet to be refined. In this review article, we will provide an update on the recent developments concerning the zoonotic potential of chlamydiae. Furthermore, we present an overview about the current state of knowledge regarding the chlamydial plasmid in terms of prevalence and significance as a virulence factor. Finally, we give insights into the progress of developing genetic tools for chlamydial species other than C. trachomatis with a special focus on zoonotic and veterinary chlamydiae.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681612","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}
Ashlesh K Murthy, Erika Wright-McAfee, Katerina Warda, Lindsay N Moy, Nhi Bui, Tarakarama Musunuri, S Manam, Clemence Z Chako, Kyle H Ramsey, Weidang Li
{"title":"Protective Anti-Chlamydial Vaccine Regimen-Induced CD4+ T cell Response Mediates Early Inhibition of Pathogenic CD8+ T cell Response Following Genital Challenge","authors":"Ashlesh K Murthy, Erika Wright-McAfee, Katerina Warda, Lindsay N Moy, Nhi Bui, Tarakarama Musunuri, S Manam, Clemence Z Chako, Kyle H Ramsey, Weidang Li","doi":"10.1093/femspd/ftae008","DOIUrl":"https://doi.org/10.1093/femspd/ftae008","url":null,"abstract":"We have demonstrated previously that TNF-α-producing CD8 + T cells mediate chlamydial pathogenesis, likely in an antigen (Ag)-specific fashion. Here we hypothesize that inhibition of Ag-specific CD8 + T cell response after immunization and/or challenge would correlate with protection against oviduct pathology induced by a protective vaccine regimen. Intranasal (i.n.) live chlamydial elementary body (EB), intramuscular (i.m.) live EB, or i.n. irrelevant antigen, bovine serum albumin (BSA), immunized animals induced near-total protection, 50% protection, or no protection, respectively against oviduct pathology following i.vag. C. muridarum challenge. In these models, we evaluated Ag-specific CD8 + T cell cytokine response at various time-periods after immunization or challenge. The results show protective efficacy of vaccine regimens correlated with reduction of Ag-specific CD8 + T cell TNF-α responses following i.vag. chlamydial challenge, not after immunization. Depletion of CD4 + T cells abrogated, whereas adoptive transfer of Ag-specific CD4 + T cells induced the significant reduction of Ag-specific CD8+ T cell TNF- α response after chlamydial challenge. In conclusion, protective anti-chlamydial vaccine regimens induce Ag-specific CD4 + T cell response that mediate early inhibition of pathogenic CD8 + T cell response following challenge and may serve as a predictive biomarker of protection against Chlamydia -induced chronic pathologies.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"24 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140841265","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":"From Fever to Action: Diagnosis, Treatment, and Prevention of Acute Undifferentiated Febrile Illnesses","authors":"Muttiah Barathan","doi":"10.1093/femspd/ftae006","DOIUrl":"https://doi.org/10.1093/femspd/ftae006","url":null,"abstract":"Acute Undifferentiated Febrile Illness (AUFI) presents a clinical challenge, often characterized by sudden fever, non-specific symptoms, and potential life-threatening implications. This review highlights the global prevalence, types, challenges, and implications of AUFI, especially in tropical and subtropical regions where infectious diseases thrive. It delves into the difficulties in diagnosis, prevalence rates, regional variations, and potential causes, ranging from bacterial and viral infections to zoonotic diseases. Furthermore, it explores treatment strategies, preventive measures, and the critical role of the One Health approach in addressing AUFI. The paper also addresses the emerging zoonotic risks and ongoing outbreaks, including COVID-19, Rickettsia spp., and other novel pathogens, emphasizing their impact on AUFI diagnosis and management. Challenges in resource-limited settings are analyzed, highlighting the need for bolstered healthcare infrastructure, enhanced diagnostics, and collaborative One Health strategies. Amidst the complexity of emerging zoonotic threats, this review underscores the urgency for a multifaceted approach to mitigate the growing burden of AUFI, ensuring early diagnosis, appropriate treatment, and effective prevention strategies.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"57 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140598553","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}
Eva Vaňková, Jaroslav Julák, Anna Machková, Klára Obrová, Anja Klančnik, Sonja Smole Možina, Vladimír Scholtz
{"title":"Overcoming antibiotic resistance: non-thermal plasma and antibiotics combination inhibits important pathogens.","authors":"Eva Vaňková, Jaroslav Julák, Anna Machková, Klára Obrová, Anja Klančnik, Sonja Smole Možina, Vladimír Scholtz","doi":"10.1093/femspd/ftae007","DOIUrl":"10.1093/femspd/ftae007","url":null,"abstract":"<p><p>Antibiotic resistance (ATBR) is increasing every year as the overuse of antibiotics (ATBs) and the lack of newly emerging antimicrobial agents lead to an efficient pathogen escape from ATBs action. This trend is alarming and the World Health Organization warned in 2021 that ATBR could become the leading cause of death worldwide by 2050. The development of novel ATBs is not fast enough considering the situation, and alternative strategies are therefore urgently required. One such alternative may be the use of non-thermal plasma (NTP), a well-established antimicrobial agent actively used in a growing number of medical fields. Despite its efficiency, NTP alone is not always sufficient to completely eliminate pathogens. However, NTP combined with ATBs is more potent and evidence has been emerging over the last few years proving this is a robust and highly effective strategy to fight resistant pathogens. This minireview summarizes experimental research addressing the potential of the NTP-ATBs combination, particularly for inhibiting planktonic and biofilm growth and treating infections in mouse models caused by methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa. The published studies highlight this combination as a promising solution to emerging ATBR, and further research is therefore highly desirable.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11094553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shan Cheng, Yi Liu, Bei He, Jinrong Zhang, Yewei Yang, Xinglv Wang, Zhongyu Li
{"title":"Chlamydia trachomatis upregulates lncRNA CYTOR to mediate autophagy through miR-206/MAPK1 axis.","authors":"Shan Cheng, Yi Liu, Bei He, Jinrong Zhang, Yewei Yang, Xinglv Wang, Zhongyu Li","doi":"10.1093/femspd/ftae011","DOIUrl":"10.1093/femspd/ftae011","url":null,"abstract":"<p><p>Chlamydia trachomatis infection can be regulated by autophagy-related genes. LncRNA CYTOR has been proven to be involved in autophagy. In this research, we investigated the role of CYTOR in autophagy induced by C. trachomatis and the potential mechanisms. After C. trachomatis infection, CYTOR and MAPK1 were up-regulated and miR-206 was down-regulated, meanwhile, the autophagy-related protein Beclin1 and LC3-Ⅱ/LC3-Ⅰ ratio were increased. Interference with CYTOR or overexpression with miR-206 downregulated the autophagy-related protein Beclin1 and the number of autophagic spots LC3, decreased the protein ratio of LC3-II/LC3-I, and upregulated the expression of P62 protein. The luciferase reporter assay confirmed that CYTOR acted as a sponge for miR-206 to target MAPK1. In addition, CYTOR promoted autophagy induced by C. trachomatis infection through the MAPK1/ERK signaling pathway activation. Taken together, we have identified a novel molecular mechanism that the CYTOR/miR-206/MAPK1 axis was involved in the regulation of autophagy in C. trachomatis infection. This work provides an experimental basis for elucidating the pathogenesis of C. trachomatis for the treatment, prevention and control of related infectious diseases.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11210502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammad Raguib Munif, Robert A Hart, Rukshan A M Rafeek, Amali C Mallawaarachchi, Lyndal Anderson, David J McMillan, Kadaba S Sriprakash, Natkunam Ketheesan
{"title":"Mechanisms that potentially contribute to the development of post-streptococcal glomerulonephritis.","authors":"Mohammad Raguib Munif, Robert A Hart, Rukshan A M Rafeek, Amali C Mallawaarachchi, Lyndal Anderson, David J McMillan, Kadaba S Sriprakash, Natkunam Ketheesan","doi":"10.1093/femspd/ftae024","DOIUrl":"10.1093/femspd/ftae024","url":null,"abstract":"<p><p>Post-streptococcal glomerulonephritis (PSGN) is primarily associated with preceding group A streptococcal skin or throat infections, now mainly observed in economically disadvantaged communities. This condition significantly predisposes individuals to later-life chronic kidney disease and concurrent renal complications, with the elderly experiencing increased severity and less favourable outcomes. Streptococcal pyrogenic exotoxin B and nephritis-associated plasmin receptor are identified nephritogenic antigens (nephritogens). Pathogenesis of PSGN is multifactorial. It can involve the formation of antigen-antibody immune complexes, causing inflammatory damage to renal glomeruli. Deposition of circulating immune complexes or in situ formation of immune complexes in glomeruli, or both, results in glomerulonephritis. Additionally, molecular mimicry is hypothesized as a mechanism, wherein cross-reactivity between anti-streptococcal antibodies and glomerular intrinsic matrix proteins leads to glomerulonephritis. Besides, as observed in clinical studies, streptococcal inhibitor of complement, a streptococcal-secreted protein, can also be associated with PSGN. However, the interplay between these streptococcal antigens in the pathogenesis of PSGN necessitates further investigation. Despite the clinical significance of PSGN, the lack of credible animal models poses challenges in understanding the association between streptococcal antigens and the disease process. This review outlines the postulated mechanisms implicated in the development of PSGN with possible therapeutic approaches.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparative analysis of genomic characteristics and immune response between Mycobacterium tuberculosis strains cultured continuously for 25 years and H37Rv.","authors":"Chuanzhi Zhu, Jing Dong, Yuheng Duan, Hongyan Jia, Lanyue Zhang, Aiying Xing, Boping Du, Qi Sun, Yinxia Huang, Zongde Zhang, Liping Pan, Zihui Li","doi":"10.1093/femspd/ftae014","DOIUrl":"10.1093/femspd/ftae014","url":null,"abstract":"<p><p>Tuberculosis (TB) continues to pose a significant global health challenge, emphasizing the critical need for effective preventive measures. Although many studies have tried to develop new attenuated vaccines, there is no effective TB vaccine. In this study, we report a novel attenuated Mycobacterium tuberculosis (M. tb) strain, CHVAC-25, cultured continuously for 25 years in the laboratory. CHVAC-25 exhibited significantly reduced virulence compared to both the virulent H37Rv strain in C57BL/6J and severe combined immunodeficiency disease mice. The comparative genomic analysis identified 93 potential absent genomic segments and 65 single nucleotide polymorphic sites across 47 coding genes. Notably, the deletion mutation of ppsC (Rv2933) involved in phthiocerol dimycocerosate synthesis likely contributes to CHVAC-25 virulence attenuation. Furthermore, the comparative analysis of immune responses between H37Rv- and CHVAC-25-infected macrophages showed that CHVAC-25 triggered a robust upregulation of 173 genes, particularly cytokines crucial for combating M. tb infection. Additionally, the survival of CHVAC-25 was significantly reduced compared to H37Rv in macrophages. These findings reiterate the possibility of obtaining attenuated M. tb strains through prolonged laboratory cultivation, echoing the initial conception of H37Ra nearly a century ago. Additionally, the similarity of CHVAC-25 to genotypes associated with attenuated M. tb vaccine positions it as a promising candidate for TB vaccine development.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phylogenetic evaluation and genotypic identification of burn-related Pseudomonas aeruginosa strains isolated from post-burn human infections during hospitalization.","authors":"Fatemeh Sanjar, Claudia P Millan, Kai P Leung","doi":"10.1093/femspd/ftae021","DOIUrl":"10.1093/femspd/ftae021","url":null,"abstract":"<p><p>Cutaneous burn trauma, compromise of dermal layers and immune defense system is a physical and fiscal burden on healthcare systems. Burn-wound infections are a serious complication of thermal injury and contribute significantly to care burden. After burn-induced trauma, sepsis by Pseudomonas aeruginosa impairs patient recovery and contributes to mortality and morbidity. Past studies show positive correlation between detection of Pseudomonas species and healing-impaired traumatic wounds. Pseudomonas aeruginosa is a resilient opportunistic human pathogen and a nosocomial agent involved in pathology of healing-impaired wounds, especially in burn patients. Expansive array of virulence determinants has resulted in gentamicin- and silver-resistant P. aeruginosa outbreaks. Knowledge of molecular dynamics and phylogeny of P. aeruginosa associated with burn wounds is limited. Therefore, we conducted whole-genome sequencing for genotyping and phylogenetic analysis of P. aeruginosa burn-associated strains (n = 19) isolated from 7 burn cases during hospitalization. Comparison of genetic features in P. aeruginosa strains in the core genome and mobilome detected genetic variations within some clonal infections over time. Genetic variations were observed among different burn cases, with some features identified in severe lung infections. Polyclonal infections were also observed, with differing genotypes and virulence potentials, highlighting the importance of reasoned sampling of isolates for clinical testing.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Omkar Indari, Subhrojyoti Ghosh, Adhiraj Singh Bal, Ajay James, Mehek Garg, Amit Mishra, Krishanpal Karmodiya, Hem Chandra Jha
{"title":"Awakening the sleeping giant: Epstein-Barr virus reactivation by biological agents.","authors":"Omkar Indari, Subhrojyoti Ghosh, Adhiraj Singh Bal, Ajay James, Mehek Garg, Amit Mishra, Krishanpal Karmodiya, Hem Chandra Jha","doi":"10.1093/femspd/ftae002","DOIUrl":"10.1093/femspd/ftae002","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) may cause harm in immunocompromised conditions or on stress stimuli. Various chemical agents have been utilized to induce the lytic cycle in EBV-infected cells. However, apart from chemical agents and external stress stimuli, certain infectious agents may reactivate the EBV. In addition, the acute infection of other pathogens may provide suitable conditions for EBV to thrive more and planting the roots for EBV-associated pathologies. Various bacteria such as periodontal pathogens like Aggregatibacter, Helicobacter pylori, etc. have shown to induce EBV reactivation either by triggering host cells directly or indirectly. Viruses such as Human simplex virus-1 (HSV) induce EBV reactivation by HSV US3 kinase while other viruses such as HIV, hepatitis virus, and even novel SARS-CoV-2 have also been reported to cause EBV reactivation. The eukaryotic pathogens such as Plasmodium falciparum and Aspergillus flavus can also reactivate EBV either by surface protein interaction or as an impact of aflatoxin, respectively. To highlight the underexplored niche of EBV reactivation by biological agents, we have comprehensively presented the related information in this review. This may help to shedding the light on the research gaps as well as to unveil yet unexplored mechanisms of EBV reactivation.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10901609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charlotte Abell-King, Alaska Pokhrel, Scott A Rice, Iain G Duggin, Bill Söderström
{"title":"Multispecies bacterial invasion of human host cells.","authors":"Charlotte Abell-King, Alaska Pokhrel, Scott A Rice, Iain G Duggin, Bill Söderström","doi":"10.1093/femspd/ftae012","DOIUrl":"10.1093/femspd/ftae012","url":null,"abstract":"<p><p>Urinary tract infection (UTI), one of the most common bacterial infections worldwide, is a typical example of an infection that is often polymicrobial in nature. While the overall infection course is known on a macroscale, bacterial behavior is not fully understood at the cellular level and bacterial pathophysiology during multispecies infection is not well characterized. Here, using clinically relevant bacteria, human epithelial bladder cells and human urine, we establish co-infection models combined with high resolution imaging to compare single- and multi-species bladder cell invasion events in three common uropathogens: uropathogenic Escherichia coli (UPEC), Klebsiella pneumoniae and Enterococcus faecalis. While all three species invaded the bladder cells, under flow conditions the Gram-positive E. faecalis was significantly less invasive compared to the Gram-negative UPEC and K. pneumoniae. When introduced simultaneously during an infection experiment, all three bacterial species sometimes invaded the same bladder cell, at differing frequencies suggesting complex interactions between bacterial species and bladder cells. Inside host cells, we observed encasement of E. faecalis colonies specifically by UPEC. During subsequent dispersal from the host cells, only the Gram-negative bacteria underwent infection-related filamentation (IRF). Taken together, our data suggest that bacterial multispecies invasions of single bladder cells are frequent and support earlier studies showing intraspecies cooperation on a biochemical level during UTI.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11180983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}