Parasite Immunology最新文献

{"title":"The Role of Innate Lymphoid Cells in the Pathogenesis of Hepatic Echinococcosis: A Literature Review.","authors":"Wei Ma, Dian Wang, Chuanchuan Liu, Haining Fan","doi":"10.1111/pim.70039","DOIUrl":"10.1111/pim.70039","url":null,"abstract":"<p><p>Hepatic echinococcosis (HE), a major zoonotic disease, remains endemic in pastoral regions of Western China, where its incidence is closely linked to geographical, livestock and sanitary conditions. The disease presents a significant clinical challenge due to the complexity of host-parasite interactions and a high recurrence rate. To date, the underlying pathogenesis and effective prevention and control strategies remain inadequately studied. Particularly, it is still unclear how innate lymphoid cells (ILCs) affect disease progression and therapeutic intervention. This review focuses on ILCs and their emerging role in the pathogenesis of HE. Through an in-depth analysis of the biological characteristics of ILCs, we revealed their significant role in immune responses and therapeutic mechanisms. Additionally, we also investigated their dynamic involvement in the development of HE. Furthermore, the specific role of gene editing in modulating ILC function was examined. Clinically, we assessed the distribution and functional status of ILCs in patients with HE and analysed their association with hepatic fibrosis and other complications. Finally, we explored novel diagnostic and therapeutic strategies based on ILC functional modulation. In short, this review highlights the critical role of ILCs in shaping the immunological landscape of HE, offering a theoretical basis for the development of ILC-targeted diagnosis and treatment of the disease. Through ILC functional modulation, the intervention of fibrotic progression and immune imbalance holds promise for overcoming current therapeutic limitations and advancing clinical translation.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 1","pages":"e70039"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12777645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912651","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":"Mechanisms of Immune Evasion, Dissemination, and Persistence in Leishmania amazonensis Infection.","authors":"Arieli Bernardo Portugal, Renato Augusto DaMatta, Edézio Ferreira da Cunha Júnior, João Luiz Mendes Wanderley","doi":"10.1111/pim.70044","DOIUrl":"10.1111/pim.70044","url":null,"abstract":"<p><p>Leishmania amazonensis is one of the etiological agents of cutaneous leishmaniasis in its localised form. Moreover, this parasite can cause more severe disease conditions, such as diffuse and disseminated cutaneous leishmaniasis. The development of more severe clinical manifestations is associated with the parasite's ability to establish a chronic infection and disseminate to cutaneous tissues distal to the site of primary infection. This ability is dependent on host immune factors but is also influenced by intrinsic factors of the parasite related to pathogenicity and evasion of the immune system. This review discusses immunological and parasitological factors associated with the latency and dissemination of L. amazonensis infection and the consequent development of severe forms of cutaneous disease.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 1","pages":"e70044"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12779597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918240","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":"Effect of Irradiated Toxocara Canis Embryonated Eggs: A Promising Vaccination Strategy.","authors":"Shreen F Ammar, Sanaa N Antonios, Rasha A Elmahy, Radwa Ismail, Amina M Salama","doi":"10.1111/pim.70059","DOIUrl":"https://doi.org/10.1111/pim.70059","url":null,"abstract":"<p><p>Toxocariasis is a global zoonotic parasitic disease caused by Toxocara canis that poses significant public health challenges. The development of a vaccine would provide a promising method to control toxocariasis. This study aimed to evaluate the protective efficacy of gamma- and UV-irradiated embryonated T. canis eggs in mice. Seventy Swiss albino mice were classified into four groups: Group (I) the normal control; Group (II) was subdivided into a positive control once (IIA) and positive control twice (IIB); Group (III) was subdivided into a gamma-vaccinated control (IIIA) and gamma-vaccinated challenged (IIIB); and Group (IV) was subdivided into a UV-vaccinated control (IVA) and UV-vaccinated challenged (IVB). On the 28th day post-infection (dpi), scanning electron microscopy, parasitological, histopathological, immunohistochemical and biochemical analyses were performed. Larval counts in the brains and livers of vaccinated mice were significantly decreased. Compared to the positive control groups, vaccinated groups exhibited fewer histopathological alterations, a reduced immunohistochemical expression of IL-1β in the brain and CD68 in the liver, and lower IL-4, IL-10 and IgE levels in both the gamma- and UV-vaccinated challenged groups. Among the two approaches, the UV-irradiated vaccine demonstrated superior protective effects. These findings suggest that vaccination with irradiated T. canis eggs, particularly with UV treatment, is a safe, efficient and cost-effective method for immunoprophylaxis against human toxocariasis.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 1","pages":"e70059"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966800","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":"CD154 Restricts Helminth-Induced Macrophage Polarisation and Proliferation While Promoting Tissue Residence.","authors":"Mariana Suárez-Martins, James Parkinson, Lili Zhang, Brian Chan, Georgia Baldwin, Rebecca J Dodd, Conor M Finlay, Pedro Papotto, Judith E Allen, Álvaro Díaz","doi":"10.1111/pim.70043","DOIUrl":"10.1111/pim.70043","url":null,"abstract":"<p><p>CD154 (CD40L) is of central importance in effector responses mediated by classically activated macrophages. However, there is limited information on the impact of CD154 on macrophage responses in type 2 contexts, characterised by IL-4-induced polarisation and proliferation. CD154 restricts the polarisation and proliferation of peritoneal cavity macrophages in response to exogenous IL-4. Here we address the impact of CD154 on peritoneal macrophages during infection of mice with the intestinal helminth Heligmosomoides polygyrus. This strictly enteric nematode causes recruitment of Th2 cells and macrophages to the peritoneal cavity alongside type 2 polarisation and proliferation of recruited and resident macrophages. Nine days post-infection, there was an increase in the expression of cell-surface CD154 in CD4⁺ T cells together with increased IL-13 levels in the cavity, suggestive of local antigen presentation. Blocking CD154 enhanced the proliferation of resident but not of recently recruited macrophages. CD154 blocking additionally potentiated the expression of type 2 marker Ym1 (Chil3) in resident and recruited macrophages. Unexpectedly, CD154 blocking caused increases in the numbers of recently recruited macrophages and the appearance of cells with characteristics of both differentiating recruited macrophages (expression of folate receptor β and MHCII) and resident macrophages (high-level expression of F4/80 and CD102). Together, these observations suggest that CD154 promotes the acquisition of tissue residence by recruited macrophages. Thus, our results indicate that in a helminth infection CD154 restricts certain aspects of the polarisation and proliferation of macrophages in response to type 2 cytokines while promoting the acquisition of resident phenotype by the recruited macrophages.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"47 12","pages":"e70043"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12701298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743800","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":"Innate Immune Recognition of Helminths: TLRs and Beyond.","authors":"Camila de Almeida Lopes, Linda Djune Yemeli, Pedro Gazzinelli-Guimaraes","doi":"10.1111/pim.70042","DOIUrl":"https://doi.org/10.1111/pim.70042","url":null,"abstract":"<p><p>Helminth parasites are complex metazoans belonging to diverse taxonomic families, each exhibiting distinct host tissue tropisms as their larval stages migrate through various tissues to complete their life cycles. Migrating larvae through the host trigger tissue disruption/damage, leading to the release of damage-associated molecular patterns (DAMPs). In addition, helminth larvae and adults release excretory/secretory factors, including proteins, lipids, nucleic acids or carry bacterial symbionts, that act as pathogen-associated molecular patterns (PAMPs), which similar to DAMPs, are sensed by innate receptors [pattern recognition receptors (PRRs), and G protein-coupled receptors (GPCRs) and others] in the skin, liver, lungs, intestines, brain, or smooth muscles, triggering localised innate inflammatory responses. The host's innate immunity plays a central role in controlling the infection and/or inducing pathogenesis. This review provides a comprehensive examination of how innate immune receptors and their host- or helminth-derived ligands regulate the control and immunopathogenesis of helminth infections, thereby advancing our understanding of the early host signalling pathways and parasite-derived factors that initiate innate immune responses.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"47 12","pages":"e70042"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708568","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":"Cytokine Profiles in Naturally Infected Cattle Reveal Immune Responses to Theileria orientalis Infection.","authors":"Vaisakhi Vikraman Sujatha, P M Deepa, R Rajasekhar, R L Rathish, A Janus","doi":"10.1111/pim.70031","DOIUrl":"https://doi.org/10.1111/pim.70031","url":null,"abstract":"<p><p>Theileria orientalis, long considered a benign haemoprotozoan, is now recognised as an emerging pathogen causing clinical theileriosis in cattle across the globe. This study investigated the clinical presentation and immunopathological responses associated with natural T. orientalis infections in northern Kerala, India. Blood samples were collected from clinically suspected (n = 52) and healthy cattle (n = 148). Infection was confirmed via Giemsa-stained blood smear examination, species-specific PCR targeting the major piroplasm surface protein (MPSP) gene, and subsequent sequencing. Among clinically suspected cases, 63.5% were smear-positive and PCR-confirmed, while subclinical infection was identified in 46.6% of healthy cattle. Morphological analysis revealed marked polymorphism of intraerythrocytic piroplasms. Clinical signs included anaemia, pyrexia, lymphadenopathy, and systemic debilitation. To elucidate host immune responses, expression levels of key pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) were quantified in peripheral blood mononuclear cells using SYBR Green-based quantitative real-time PCR. Clinically affected animals exhibited significantly elevated expression of IL-6 and IL-1β (p < 0.05), indicative of a heightened inflammatory response, whereas TNF-α expression showed a non-significant downward trend. Correlation analysis revealed that parasite burden was positively associated with IL-6 and IL-1β expression but not with TNF-α, linking parasite load to the inflammatory response. The suppressed TNF-α response suggests a possible immune evasion strategy unique to T. orientalis, contrasting with the elevated TNF-α typically seen in T. annulata and T. parva infections. These findings indicate that IL-6 and IL-1β may serve as potential biomarkers of severe oriental theileriosis. These findings provide new insights into the immunopathogenesis of oriental theileriosis and suggest that cytokine dysregulation contributes to clinical disease severity. Furthermore, the high prevalence of subclinical infections underscores the role of carrier animals in sustaining transmission cycles, complicating disease control efforts in endemic regions. This study highlights the need for improved diagnostic strategies and targeted immunomodulatory interventions in managing T. orientalis infections.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"47 11","pages":"e70031"},"PeriodicalIF":2.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145401519","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":"Osteopontin Promotes Liver Echinococcus multilocularis Growth and Invasion via p38MAPK Pathway.","authors":"Gang Xu, Yi Mao, Zhi-Hua Zhang, Jin You, Chang-Jia Li, Zhi-Chao Wu, Shi-Wei Xie, Shuai Hu, Yu-Fei Ge, Zhi Xu, Yu-Meng Zhang, Li-Hua Rong, Xiao-Hu Yin, Shi-Jie Zhang, Xu Zhang","doi":"10.1111/pim.70041","DOIUrl":"https://doi.org/10.1111/pim.70041","url":null,"abstract":"<p><p>This study aimed to elucidate how osteopontin (OPN) affects the growth, invasion, and extrahepatic metastasis of Echinococcus multilocularis (Em) through the p38MAPK signalling pathway of host hepatocytes. C57BL/6J mice were randomly divided into the control group (n = 10), the LV-OPN-0423 group (n = 10), the anti-p38MAPK group (n = 10), and the anti-p38MAPK + LV-OPN-0423 group (n = 10). Em infection models in mice were set up. The mice were fed for 6 weeks under suitable conditions. The mice in the anti-p38MAPK group and the anti-p38MAPK + LV-OPN-0423 group were then given SB202190 (this is an inhibitor of p38MAPK) for 4 weeks, and the mice in each group were injected with corresponding lentivirus diluent once a week for 8 weeks. After the intervention was completed, the liver volume and weight were measured, and the liver was embedded in paraffin and sectioned. Sections were subjected to haematoxylin and eosin (HE), periodic acid-Schiff (PAS), and immunohistochemical staining to observe the growth and invasion of Em, as well as the expression levels of OPN, p38MAPK, and p-p38MAPK of the host. SB202190 hindered Em's growth, invasion, and migration. The level of OPN facilitated Em's growth, invasion, and migration, which can be reversed by SB202190. The OPN level promoted the expression of p38MAPK and p-p38MAPK. These results suggested that OPN could regulate Em's growth and metastasis through the p38MAPK signalling pathway in host hepatocytes, providing evidence that OPN and p38MAPK may be novel molecular targets for treating alveolar echinococcosis.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"47 11","pages":"e70041"},"PeriodicalIF":2.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534036","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":"Comparison of Platelet Functions, Plasma Proteins and Lipids in Filarial and Non-Filarial Edema Patients.","authors":"Sushil Surtani, Ashutosh Kumar, Alka Singh, Mumtaz Ahmad Ansari, Jyotsna Kailashiya","doi":"10.1111/pim.70037","DOIUrl":"https://doi.org/10.1111/pim.70037","url":null,"abstract":"<p><p>Lymphatic filariasis results in chronic edema, pain, elephantiasis and disfigurement in humans. It was previously reported that platelet aggregation is inhibited in lymphatic filariasis patients, compared to healthy controls. However, it was not clear whether the inhibition was due to filarial parasite infection or due to the presence of edema. This study was planned to compare platelet functions, plasma proteins and lipids in filarial and non-filarial edema patients. Edema patients were tested for the presence of filarial antigens and antibodies in their blood and were grouped as filarial and non-filarial edema patients accordingly. Platelet aggregation, size distribution, platelet activation markers, plasma proteins and lipids were measured in collected blood samples. Results showed that platelet aggregation was significantly inhibited in filarial edema patients, compared to non-filarial edema patients. Soluble P-selectin and beta thromboglobulin showed significant positive correlation with each other only in non-filarial edema patients. Plasma total cholesterol was lower in filarial edema patients, and HDL was lower in only female filarial edema patients. Observations confirm that inhibition of platelet functions is due to filarial parasite infection, not merely due to the presence of edema. Results also indicate uncoupling and disturbances of platelet activation processes.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"47 11","pages":"e70037"},"PeriodicalIF":2.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145409196","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":"Serum Concentrations of Th1, Th2 and Treg-Associated Cytokines in Patients With Ocular Toxoplasmosis.","authors":"Ovi Sofia, Rahajeng Anugrahing Saldianovitta, I Nyoman Surya Ari Wahyudi, Loeki Enggar Fitri, Hani Susianti, Seskoati Prayitnaningsih, Hidayat Sujuti","doi":"10.1111/pim.70040","DOIUrl":"https://doi.org/10.1111/pim.70040","url":null,"abstract":"<p><p>Ocular toxoplasmosis (OT) is a common cause of posterior uveitis worldwide, primarily caused by Toxoplasma gondii. The immune response plays a crucial role in OT pathogenesis. However, a study using aqueous humour samples has limited applicability due to the invasive procedure. This study used peripheral blood samples to compare the concentrations and ratios of cytokines involved in Th1, Th17 and Treg immune responses between OT patients and seropositive individuals without ocular lesions (SP) who met the inclusion criteria. The ELISA method was used to measure cytokine concentrations, and the cytokine ratio was determined by comparing the concentration of two cytokines. This study revealed the differences in the concentrations of IL-17 (p = 0.015), IFN-α (p = 0.015) and IL-6 (p = < 0.001) between OT and SP groups, as well as the ratio of IFN-α/TGF-β (p = 0.012), IFN-β/TGF-β (p = 0.020), IL-17/TGF-β (p = 0.018), TNF-α/TGF-β (p = 0.015), IL-17/IL-6 (p = 0.003), IL-6/IFN-γ (p = < 0.001) and IL-6/TNF-α (p = < 0.001). Among the variables, the IFN-α concentrations and IL-6/TNF-α ratio were the most significant factors influencing the risk of OT. The novel findings of this study regarding the involvement of IFN-α in the pathogenesis of OT are considered important and have the potential to reveal a predictive factor for the occurrence of OT in humans.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"47 11","pages":"e70040"},"PeriodicalIF":2.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145459473","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":"Impact of IL-6 Promotor AnTn Polymorphism on Blood IL-6 Levels and Pregnancy Outcome in Toxoplasma gondii Infected Women.","authors":"Muhammad Bar Khan, Sanaullah Khan, Khair Rafiq, Muhammad Fawad Khan, Muhammad Yaqoob, Muhammad Adnan","doi":"10.1111/pim.70038","DOIUrl":"10.1111/pim.70038","url":null,"abstract":"<p><p>Toxoplasma gondii is a protozoan parasite causing Toxoplasmosis in humans. Interleukin-6 (IL-6) is a multifunctional cytokine that controls infection and helps maintain pregnancy. The study investigated the impact of IL-6 promoter polymorphism on blood IL-6 levels and pregnancy outcomes in T. gondii-infected women. A cross-sectional study was conducted on 244 women, including 83 infected in Group 1 (Group 1a = 43, Group 1b = 40), 81 uninfected with RPL (Group 2), and 80 controls (Group 3). Blood and placental tissue samples were collected, and screened for IL-6 levels using ELISA. The DNA was isolated, amplified for T. gondii DNA and the IL-6 gene by PCR, and the IL-6 gene was sequenced using the Sanger method. The genotypic (p < 0.001) and allelic (p < 0.001) frequencies were significantly variable. Highly prevalent genotypes were A10T11/A10T11 in Group 1a (28%), A9T11/A9T11 in Group 1b (27.5%) and Group 2 (33.3%), while A8T12/A10T10 and A10T10/A10T10 were in Group 3 (20% each). The mean blood IL-6 levels were significantly variable in all the study groups (p < 0.0001). The A9T11/A9T11 genotype was significantly linked with high IL-6 levels, while the A10T10/A10T11, A10T11/A10T11 and A10T10/A10T10 genotypes were associated with low IL-6 levels. In conclusion IL-6 AnTn polymorphism is associated with changed IL-6 levels and RPL in women infected by T. gondii.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"47 11","pages":"e70038"},"PeriodicalIF":2.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145489955","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}