Gnohion Fabrice Somé, Modou Séré, Bienvenu Martin Somda, Guiguigbaza-Kossigan Dayo, Georges Anicet Ouédraogo, Alain Boulangé, Ghizlane Maarifi, Isabelle Chantal, David Berthier-Teyssedre, Sophie Thévenon
{"title":"Immune Response in Cattle Trypanosomosis and Trypanotolerance: Main Findings and Gaps.","authors":"Gnohion Fabrice Somé, Modou Séré, Bienvenu Martin Somda, Guiguigbaza-Kossigan Dayo, Georges Anicet Ouédraogo, Alain Boulangé, Ghizlane Maarifi, Isabelle Chantal, David Berthier-Teyssedre, Sophie Thévenon","doi":"10.1111/pim.13075","DOIUrl":"https://doi.org/10.1111/pim.13075","url":null,"abstract":"<p><p>Trypanosome parasites of the genus Trypanosoma cause African animal trypanosomosis, a devastating livestock disease plaguing sub-Saharan Africa. Unlike many protozoan parasites, these extracellular blood-borne pathogens directly engage the host's immune system. While the mouse model has provided valuable insights, a comprehensive understanding of the bovine immune response to trypanosomes remains elusive. Addressing the immune response in cattle, the most relevant host species, and how it takes part in mitigating the negative impact of the disease could contribute to setting up sustainable control strategies. This review summarises the current knowledge of the immune response in cattle during trypanosomosis. Following a brief overview of infection processes and bovine trypanotolerance, we present advances in the regulation of host innate, inflammatory and adaptive responses and delve into the key immunological players involved in immunoactivities and immunosuppression. We discuss how these mechanisms contribute to tolerance or susceptibility to infection, highlighting critical gaps in knowledge that require further investigation.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"46 11","pages":"e13075"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605726","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}
Alshimaa M Elmalawany, Gamalat Y Osman, Azza H Mohamed, Fatema M Khalaf, Rania I Yassien
{"title":"Schistosomicidal Effects of Moringa oleifera Seed Oil Extract on Schistosoma mansoni-Infected Mice.","authors":"Alshimaa M Elmalawany, Gamalat Y Osman, Azza H Mohamed, Fatema M Khalaf, Rania I Yassien","doi":"10.1111/pim.13070","DOIUrl":"10.1111/pim.13070","url":null,"abstract":"<p><p>Schistosomiasis causes severe hepatic fibrosis, making it a global health issue. Moringa oleifera seed oil extract, which had antiparasitic, anti-inflammatory and antioxidant effects, was investigated as an alternative treatment. The 50 mice were divided into control, infected, praziquantel-treated, M. oleifera seed oil extract-treated and combined treatment groups. These treatments were examined for their effects on egg granulomas, hepatic enzymes, total protein, albumin, antioxidant enzymes and pro-inflammatory cytokines. M. oleifera seed oil and/or PZQ significantly reduced egg numbers, granuloma size and liver histopathology. M. oleifera seed oil reduced hepatic enzyme activity, increased total protein and albumin, and increased antioxidant enzyme activity while decreasing malondialdehyde. M. oleifera seed oil reduced the levels of pro-inflammatory cytokines. M. oleifera seed oil may treat schistosomiasis instead of PZQ due to its antifibrotic, immunomodulatory and schistosomicidal properties.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"46 11","pages":"e13070"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569338","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}
Hadis Gandomkar, Mostafa Changaei, Mir Mohammadreza Hosseini, Sara Soudi, Ahmad Zavaran Hosseini
{"title":"C57BL/6 Peritoneal Macrophage Exosomes Improve Antileishmanial Functions of the RAW264.7 Cells.","authors":"Hadis Gandomkar, Mostafa Changaei, Mir Mohammadreza Hosseini, Sara Soudi, Ahmad Zavaran Hosseini","doi":"10.1111/pim.13069","DOIUrl":"https://doi.org/10.1111/pim.13069","url":null,"abstract":"<p><p>Leishmaniasis is considered one of the most critical health concerns in the world. Unfortunately, no protective vaccines exist and conventional treatments are relatively ineffective. Therefore, new strategies are necessary against leishmaniasis. In recent years, exosomes have shown promising therapeutic outcomes in various diseases, including infectious diseases. In this regard, we aimed to explore the effect of the exosome, pyrimethamine and their combination on the anti-parasitic function of RAW264.7 cells against Leishmania major. Exosomes were isolated from the C57BL/6 peritoneal macrophages. L. major infected and non-infected RAW264.7 cells treated with exosomes, pyrimethamine (PM), and exosomes along with PM. The effect of the treatments was analysed on phagocytosis, efferocytosis, the intracellular parasite count, arginase activity, nitric oxide (NO) and reactive oxygen species (ROS) production. Exosomes could significantly elevate the phagocytosis, efferocytosis, NO and ROS in both infected and non-infected groups (Pv < 0.05). The exosomes reduced the arginase activity in both groups (Pv < 0.05). The intracellular parasite count was significantly lower after treatment with exosomes (Pv < 0.05). These results demonstrate that MQ-derived exosomes can enhance in vitro anti-parasitic responses against L. major. This provides a potential pathway for more effective treatments and underscores the importance of further research in this area.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"46 10","pages":"e13069"},"PeriodicalIF":1.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472181","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":"Correction to \"Improving the Immunogenicity and Protective Efficacy of a Whole-Killed Malaria Blood-Stage Vaccine by Chloroquine\".","authors":"","doi":"10.1111/pim.13065","DOIUrl":"https://doi.org/10.1111/pim.13065","url":null,"abstract":"","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"46 10","pages":"e13065"},"PeriodicalIF":1.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366171","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":"Effects of Amphotericin B-Conjugated Functionalized Carbon Nanoparticles in the Treatment of Cutaneous Leishmaniasis.","authors":"Maryam Heidari-Kharaji, Suisha Suruwb Guerra, Robinson Pavene Puneiad","doi":"10.1111/pim.13068","DOIUrl":"https://doi.org/10.1111/pim.13068","url":null,"abstract":"<p><p>Leishmaniasis is a parasitic disease spread by the bite of an infected sandfly and caused by protozoan parasites of the genus Leishmania. Currently, there is no vaccine available for leishmaniasis in humans, and the existing chemotherapy methods face various clinical challenges. The majority of drugs are limited to a few toxic compounds, with some parasite strains developing resistance. Therefore, the discovery and development of a new anti-leishmanial compound is crucial. One promising strategy involves the use of nanoparticle delivery systems to accelerate the effectiveness of existing treatments. In this study, Amphotericin B (AmB) was incorporated into functionalized carbon nanotube (f-CNT) and evaluated for its efficacy against Leishmania major in vitro and in a BALB/c mice model. The increase in footpad thickness was measured, and real-time PCR was used to quantify the parasite load post-infection. Levels of nitric oxide and cytokines IL-4 and IFN-γ were also determined. We found that f-CNT-AmB significantly reduced the levels of promastigotes and amastigotes of the Leishmania parasite. The nanoparticle showed strong anti-leishmanial activity with an IC<sub>50</sub> of 0.00494 ± 0.00095 mg/mL for promastigotes and EC<sub>50</sub> of 0.00294 ± 0.00065 mg/mL for amastigotes at 72 h post-infection, without causing harm to mice macrophages. Treatment of infected BALB/c mice with f-CNT-AmB resulted in a significant decrease in cutaneous leishmania (CL) lesion size in the foot pad, as well as reduced Leishmania burden in both lymph nodes and spleen. The levels of nitric oxide and IFN-γ significantly increased in the f-CNT-AmB treated groups. Also, our results showed that the level of IL-4 significantly decreased after f-CNT-AmB treatment in comparison to other groups. In conclusion, our results demonstrate that AmB loaded into f-CNT is significantly more effective than AmB alone in inhibiting parasite propagation and promoting a shift towards a Th1 response.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"46 10","pages":"e13068"},"PeriodicalIF":1.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372515","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}
Marilene Oliveira Dos Santos, Sidnei Ferro Costa, Gabriela Torres Rebech, Jéssica Henrique de Freitas, Jaqueline Poleto Bragato, Matheus Fujimura Soares, Lucas Takeshi Siqueira Ito, Flavia de Rezende Eugênio, Paulo Sérgio Patto Dos Santos, Valéria Marçal Felix de Lima
{"title":"Interleukin-27 Regulates Adaptative Immune Responses Associated With Control of Parasite Replication in Canine Leishmaniasis.","authors":"Marilene Oliveira Dos Santos, Sidnei Ferro Costa, Gabriela Torres Rebech, Jéssica Henrique de Freitas, Jaqueline Poleto Bragato, Matheus Fujimura Soares, Lucas Takeshi Siqueira Ito, Flavia de Rezende Eugênio, Paulo Sérgio Patto Dos Santos, Valéria Marçal Felix de Lima","doi":"10.1111/pim.13063","DOIUrl":"https://doi.org/10.1111/pim.13063","url":null,"abstract":"<p><p>Interleukin 27 (IL-27) is a cytokine that regulates susceptibility to Leishmania infantum infection in humans and experimental models. This cytokine has not yet been described in canine leishmaniasis (CanL). Therefore, we investigated whether IL-27 has a regulatory role in CanL. The EBI3 and p28 subunits of IL-27 were measured in splenic leukocytes culture supernatant from dogs with CanL and compared to control dogs. We also correlated EBI3 and p28 levels with IL-21, anti-L. infantum antibodies and parasite loads. We performed functional assays followed by IL-27 blockade and measured parasite loads, production of cytokines in splenic leukocytes culture supernatant, and the expression of PD-1, CTLA-4, phospho-Stat-1/3, T-bet, GATA3 and nitric oxide production (NO). Both IL-27 subunits increased in the supernatant of dogs with CanL compared to control dogs. EBI3 and p28 levels showed a moderate positive correlation with IL-21 (r = 0.67, p < 0.0001 and r = 0.45, p < 0.012, respectively), and the EBI3 subunit was positively associated with anti-L. infantum IgG antibodies (r = 0.38, p < 0.040) and parasite load (r = 0.47, p < 0.009). IL-27 and IL-21 participate of immune responses in CanL. IL-27 may be associated with the failure of immunity to control parasite replication via upregulation of the expression of PD-1, CTLA-4, T-bet and NO in splenic leukocytes from dogs with CanL. These findings suggest that the pathways regulated by IL-27 are involved in CanL pathogenesis in the host, and may be targets for new therapies.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"46 10","pages":"e13063"},"PeriodicalIF":1.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366172","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}
Zeynep Islek, Mehmet Hikmet Ucisik, Fikrettin Sahin
{"title":"Astrocytes Can Be Key Players Against Cerebral Leishmaniasis: In Vitro Co-Culture Model for the Assessment of Infection.","authors":"Zeynep Islek, Mehmet Hikmet Ucisik, Fikrettin Sahin","doi":"10.1111/pim.13071","DOIUrl":"https://doi.org/10.1111/pim.13071","url":null,"abstract":"<p><p>Leishmaniasis is a neglected tropical disease, caused by protozoan parasites of Leishmania (L.), and is transmitted by bite of phlebotomine sandflies. There are several studies on central nervous system infection to indicate that Leishmania can cross the blood-brain barrier, resulting in neurological manifestations, known as \"cerebral leishmaniasis.\" This study highlighted the notions: (i) polarisation of bone marrow-derived macrophages (BMDM) incubated following stimulation with lipopolysaccharide (LPS) or soluble Leishmania antigen (SLA), (ii) quantification of parasites within co-culture of Leishmania-infected macrophages, and astrocytes, and (iii) effect of interferon-gamma (IFN-γ) on the infection rate of co-culture populations. Accordingly, 83% of overall macrophage population was identified on day 7 for CD11b and F4/80 macrophage markers. Flow cytometry analysis revealed significant increases in CD11b and F4/80 surface markers in LPS and SLA-stimulated BMDMs at 24 h, compared to untreated cells. TNF-α levels increased significantly in both LPS and SLA-treated BMDMs after 48 h. Additionally, SLA treatment induced a more elongated, spindle-like shape in the cells, indicative of M2 macrophage polarisation over the M1 phenotype. When non-infected astrocytes with/without stimulation with IFN-γ before co-culture, gp63 FITC-labelled parasite populations (%) in co-culture decreased to 25% at 72 h, thus indicating a lower infection rate in a time-dependent manner. IFN-γ and IL-6 levels significantly increased to 71.66 ± 3.51 and 184 ± 14.42 pg/mL, resulting in the inflammatory response in the co-culture system at 48 h (p ≤ 0.0001), when compared to the control (30 ± 2.52 pg/mL for IFN-γ and 8.66 ± 2.37 pg/mL for IL-6) at 0 h of the incubation. It is the first study to emphasize the communication between Leishmania-infected macrophages and astrocytes regarding Leishmania parasite load. The results suggest that astrocytes can lead to the reduction in Leishmania parasites, thereby controlling the incidence of cerebral leishmaniasis.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"46 10","pages":"e13071"},"PeriodicalIF":1.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505714","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}
Ludoviko Zirimenya, Agnes Natukunda, Jacent Nassuuna, Joyce Kabagenyi, Gyaviira Nkurunungi, Alison M Elliott, Emily L Webb
{"title":"The Effect of Malaria on Responses to Unrelated Vaccines in Animals and Humans: A Systematic Review and Meta-Analysis.","authors":"Ludoviko Zirimenya, Agnes Natukunda, Jacent Nassuuna, Joyce Kabagenyi, Gyaviira Nkurunungi, Alison M Elliott, Emily L Webb","doi":"10.1111/pim.13067","DOIUrl":"10.1111/pim.13067","url":null,"abstract":"<p><p>Vaccine efficacy varies globally, often showing reduced immune responses in low- and middle-income countries, possibly due to the immunomodulatory effects of parasitic infections like malaria. This systematic review evaluates the impact of malaria on immune responses to unrelated vaccines in humans and animals. We systematically searched five databases-MEDLINE, Web of Science, Global Health, Scopus and Embase-up to 5th December 2023. Eligible studies compared immune responses to WHO-approved vaccines between malaria-infected and uninfected groups, or between antimalarial-treated and untreated groups. Meta-analysis was performed using random-effects models with standardised mean differences (SMDs) as summary statistics. The study is registered with PROSPERO (CRD42022298053). Twenty-four articles (17 human, 7 animal) met the inclusion criteria, with 13 human articles contributing data for the meta-analysis. Significant heterogeneity was observed. Vaccine responses were higher in malaria uninfected individuals (SMD 0.34, 95% CI 0.07 to 0.60, I<sup>2</sup> = 87.15%) with weaker differences between antimalarial-treated and untreated groups (SMD 0.07, 95% CI -0.01 to 0.16, I<sup>2</sup> = 85.01%). The overall SMD for malaria uninfected/treated vs. infected/untreated was 0.15, 95% CI 0.05-0.26, I<sup>2</sup> = 90.91. Narrative analysis suggested malaria's adverse impact on vaccine responses in animals. Malaria infection may impair vaccines responses; with preventive treatment of malaria partially reversing these effects, highlighting the need for targeted public health interventions.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"46 10","pages":"e13067"},"PeriodicalIF":1.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505715","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}
Parasite ImmunologyPub Date : 2024-09-13DOI: 10.1111/j.1365-3024.1998.tb00001.x
A. LANE, D. BOULANGER, G. RIVEAU, A. CAPRON, R.A. WILSON
{"title":"Murine immune responses to Schistosoma haematobium and the vaccine candidate rSh28GST","authors":"A. LANE, D. BOULANGER, G. RIVEAU, A. CAPRON, R.A. WILSON","doi":"10.1111/j.1365-3024.1998.tb00001.x","DOIUrl":"https://doi.org/10.1111/j.1365-3024.1998.tb00001.x","url":null,"abstract":"SUMMARY<jats:italic>Longitudinal studies of</jats:italic> Schistosoma haematobium <jats:italic>infection in CBA mice revealed a progressive down‐regulation of cellular immune responses, as measured by mitogenic and antigenic stimulation of</jats:italic> in vitro <jats:italic>lymphocyte cultures. Antigen‐stimulated production of the Th1 cytokine IFN‐γ by splenocytes increased progressively up to 14 weeks post infection, (four weeks after the onset of parasite egg production), before declining swiftly. Levels of the Th2 cytokine IL‐4 in the same cultures remained low until 14 weeks, after which they rose rapidly as IFN‐γ declined. High levels of IL‐10 coincided with the peak in IFN‐γ production, suggesting a non Th2‐restricted role for this cytokine. Both total and antigen‐specific immunoglobulin production confirmed parasite egg deposition as being a major stimulus for host humoral responses. The</jats:italic> S. haematobium tobium <jats:italic>infection failed to elicit detectable T cell responses to the antifecundity vaccine candidate rSh28GST. However, low levels of antibody were detectable in infected mouse serum and strong IgG and IgA production was induced by vaccination with rSh28GST plus adjuvant.</jats:italic>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"10 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247827","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":"SEA Alleviates Hepatic Ischaemia-Reperfusion Injury by Promoting M2 Macrophage Polarisation.","authors":"Shudong Xie, Chen Guo, Pengpeng Zhang, Junhui Li, Yu Zhang, Chen Zhou, Xiaofei Fan, Yingzi Ming","doi":"10.1111/pim.13061","DOIUrl":"10.1111/pim.13061","url":null,"abstract":"<p><p>Hepatic ischaemia-reperfusion (I/R) injury is a frequent and nearly inevitable pathophysiological process without widely accepted effective therapy. Soluble egg antigen (SEA) of Schistosoma japonicum (S. japonicum) is the main mediators capable of regulating immunological activities and has received increased attention in immune-mediated diseases. But its role in hepatic I/R injury has not been well defined. This study aimed to elucidate whether SEA protects liver against hepatic I/R injury and explore underlying mechanism. After intraperitoneal injecting SEA three times a week for 4 weeks, mice underwent 70% hepatic I/R injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), haematoxylin-eosin (HE) and TdT-mediated dUTP nick-end labelling (TUNEL) staining were used to evaluate liver injury. The severity related to the inflammatory response was also investigated. Furthermore, immunofluorescence was used to detect macrophage polarisation. Compared with the hepatic I/R injury group, SEA pretreatment significantly alleviated hepatic I/R injury induced liver damage, apoptosis and inflammatory. Interestingly, SEA enhanced the polarisation of macrophages towards M2 macrophages in vivo. We are the first to investigate the therapeutic efficacy of S. japonicum SEA in a hepatic I/R injury model in mice. We provided the first direct evidence that SEA attenuated hepatic I/R injury by promoting M2 macrophage polarisation.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"46 8-9","pages":"e13061"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308343","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}