Journal of Pharmacy and Pharmacology最新文献

{"title":"Development of a pharmacokinetic/pharmacodynamic evaluation model for osteomyelitis and usefulness of tedizolid as an alternative to vancomycin against MRSA osteomyelitis.","authors":"Xiaoxi Liu, Yuki Enoki, Kazuaki Taguchi, Kazuaki Matsumoto","doi":"10.1093/jpp/rgae124","DOIUrl":"https://doi.org/10.1093/jpp/rgae124","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to develop a suitable osteomyelitis model for pharmacokinetic/pharmacodynamic (PK/PD) evaluation and to investigate the target PK/PD values of vancomycin and tedizolid against methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis.</p><p><strong>Methods: </strong>An osteomyelitis model was established by implanting an MRSA-exposed sterilized suture in the tibia of normal mice and mice with cyclophosphamide-induced neutropenia. The suitability of the osteomyelitis mouse model for PK/PD evaluation was assessed using vancomycin as an indicator. The target PK/PD values for tedizolid were determined using this model.</p><p><strong>Key findings: </strong>In neutropenic mice, to achieve a static effect and 1 log10 kill against MRSA, the ratios of the area under the free drug concentration-time curve for 24 h to the minimum inhibitory concentration (fAUC24/MIC) of vancomycin were 91.29 and 430.03, respectively, confirming the validity of the osteomyelitis model for PK/PD evaluation. In immunocompetent mice, the target fAUC24/MIC values of tedizolid for achieving a static effect and 1 log10 kill against MRSA were 2.40 and 49.20, respectively. Additionally, only a 0.28 log10 kill was achieved in neutropenic mice with 20 times the human equivalent dose of tedizolid.</p><p><strong>Conclusions: </strong>In patients with restored immunity, tedizolid can potentially be used as an alternative to intravenous vancomycin therapy.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590863","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":"Shikonin mitigates cyclophosphamide-induced cardiotoxicity in mice: the role of sirtuin-1, NLRP3 inflammasome, autophagy, and apoptosis.","authors":"Fatemah A Alherz, Asmaa Saleh, Mona Y Alsheikh, Hany M Borg, Ahmed M Kabel, Maaly A Abd Elmaaboud","doi":"10.1093/jpp/rgae119","DOIUrl":"10.1093/jpp/rgae119","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study was to elucidate the protective potential of shikonin (SHK) on cyclophosphamide (CP)-induced cardiotoxicity in Swiss albino mice.</p><p><strong>Methods: </strong>Mice received SHK in three different doses by oral gavage daily for 14 days and CP at 100 mg/kg, intraperitoneally once on the seventh day. On the 15th day, mice were euthanized, blood collected, and hearts were removed to estimate various biochemical and histopathological parameters.</p><p><strong>Key findings: </strong>CP significantly increased serum lactate dehydrogenase, creatine kinase-MB, troponin I and NT pro-BNP, and cardiac malondialdehyde and decreased cardiac total antioxidant capacity and Nrf2, whereas increased inflammatory markers in the cardiac tissues. CP also caused hypertrophy and fibrosis in the cardiac tissues via activation of IL6/JAK2/STAT3 while depressed SIRT1 and PI3K/p-Akt pathway with consequent increased apoptosis and dysregulation of autophagy. SHK treatment reversed these changes in a dose-dependent manner and showed a significant protective effect against CP-induced cardiotoxicity via suppressing oxidative stress, inflammation, and apoptosis with modulation of autophagy via induction of SIRT1/PI3K/p-Akt signaling.</p><p><strong>Conclusions: </strong>Shikonin may be used as an adjuvant to cyclophosphamide in cancer treatment, but further research is needed to investigate its effects on cardiotoxicity in distinct animal cancer models.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154378","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":"The anti-rheumatoid arthritic activity of Artemisia ordosica Krasch. (traditional Chinese/Mongolian medicine) extract in collagen-induced arthritis in rats.","authors":"Xiao-Yan Han, Ya-Ru Han, Hao-Yu Xu, Ya-Wei Hu, Xiao-Yan Yan, Guan-Hua Du, Zhan-Fei She, Bin Xiao","doi":"10.1093/jpp/rgae097","DOIUrl":"10.1093/jpp/rgae097","url":null,"abstract":"<p><strong>Objectives: </strong>Rheumatoid arthritis (RA) seriously affects the daily life of people. The whole plant of Artemisia ordosica Krasch. (AOK) has been used in folk medicine. This study aimed to investigate the in vivo anti-RA effects of AOK extract (AOKE) on collagen-induced arthritis in rats.</p><p><strong>Methods: </strong>AOKE (400, 200, or 100 mg/kg) was administered orally to animals for 30 days. Body weight, paw swelling, arthritis index, thymus, and spleen indices, and pathological changes were assessed for effects of AOKE on RA. Furthermore, the inflammatory cytokines in rat serum were detected. In addition, the expressions of STAT3, Caspase-3, Galectin-3, and S100A9 in synovial tissue were researched using immunohistochemistry.</p><p><strong>Key findings: </strong>The AOKE significantly reduced the arthritis indices, paw swelling, spleen, and thymus indices. Meanwhile, AOKE (400 mg/kg) decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-17A, and increased the level of IL-10 in rat serum. Histopathological examination showed that AOKE reduced inflammatory cell infiltration and cartilage erosion. Then, AOKE decreased the expressions of STAT3, Galectin-3, S100A9, and increased the expression of Caspase-3.</p><p><strong>Conclusion: </strong>AOKE had interesting anti-RA activity in rats, which deserved further research for the development and clinical use of this medicinal resource.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141766420","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":"Evaluating the protective effect of dapsone on experimental osteoarthritis models induced by MIA in male rats.","authors":"Kimia Nazari, Saereh Hosseindoost, Ahmad Reza Dehpour, Yasaman Kheirandish, Hamed Shafaroodi","doi":"10.1093/jpp/rgae087","DOIUrl":"10.1093/jpp/rgae087","url":null,"abstract":"<p><strong>Objectives: </strong>Osteoarthritis, a degenerative condition that results in significant morbidity, is typically managed with treatments aimed at symptom relief rather than addressing the underlying degeneration. Dapsone, recognized for its anti-inflammatory, antioxidant, antiexcitotoxic, and antiapoptotic properties, has demonstrated promising effects in various neurodegenerative diseases. This study explores the potential of dapsone to mitigate articular destruction, inflammation, and pain in rat models of osteoarthritis.</p><p><strong>Methods: </strong>Osteoarthritis was induced in rats by injecting MIA into the right knee joint. Dapsone was then administered intraperitoneally at 5, 10, or 20 mg/kg every 2 days for 2 weeks. Behavioural tests were done on days 0, 7, and 14. On day 14, the articular cartilage was histologically analysed using H&E staining. Serum levels of NF-kB, IL-1β, and TNF-α were evaluated by ELISA.</p><p><strong>Results: </strong>Dapsone effectively reduces pain, inflammation, and articular cartilage damage in osteoarthritis. Specifically, it improves mechanical allodynia and thermal hyperalgesia, reduces inflammatory markers (TNF-α, IL-1β, and NF-κB), and protects against cartilage destruction and chondrocyte loss, with the most significant effects at 20 mg/kg.</p><p><strong>Conclusions: </strong>Dapsone effectively prevents pain, inflammation, and cartilage damage in osteoarthritis rats, suggesting its potential as a therapeutic option for managing osteoarthritis.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889572","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: Evaluating the protective effect of dapsone on experimental osteoarthritis models induced by MIA in male rats.","authors":"","doi":"10.1093/jpp/rgae128","DOIUrl":"10.1093/jpp/rgae128","url":null,"abstract":"","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348961","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":"Inhalation of Curcumae Rhizoma volatile oil attenuates depression-like behaviours via activating the Nrf2 pathway to alleviate oxidative stress and improve mitochondrial dysfunction.","authors":"Meixizi Lai, Dan Su, Zhifu Ai, Ming Yang, Zhentao Zhang, Qi Zhang, Wenxiang Shao, Tao Luo, Genhua Zhu, Yonggui Song","doi":"10.1093/jpp/rgae082","DOIUrl":"10.1093/jpp/rgae082","url":null,"abstract":"<p><strong>Objectives: </strong>Curcumae Rhizoma (CR) is a traditional Chinese medicine used frequently in clinics, which contains volatile components that exhibit various active effects. This study explores the effect of Curcumae Rhizoma volatile oil (CRVO) on depressive mice and its possible mechanism of action.</p><p><strong>Methods: </strong>Chemical composition of CRVO was analysed by GC-MS. DPPH and ABTS free radical scavenging assays were used to evaluate the in vitro antioxidant capacity of CRVO. A chronic unpredictable mild stress (CUMS) model was used to evaluate the antidepressant effect of CRVO. The effects of CRVO on oxidative stress in vivo were investigated using Nissl staining, ELISA and transmission electron microscopy. The Nrf2/HO-1/NQO1 signalling pathway was detected by western blotting and immunofluorescence. ML385, a Nrf2 inhibitor was used to validate the effect of Nrf2 on CUMS mice with CRVO treatment.</p><p><strong>Key findings: </strong>Phytochemical analysis showed that CRVO is rich in its characteristic components, including curzerene (31.1%), curdione (30.56%), and germacrone (12.44%). In vivo, the administration of CRVO significantly ameliorated CUMS-induced depressive-like behaviours. In addition, inhalation of CRVO significantly alleviated the oxidative stress caused by CUMS and improved neuronal damage and mitochondrial dysfunction. The results of mechanistic studies showed that the mechanism of action is related to the Nrf2/HO-1/NQO1 pathway and the antioxidant and antidepressant effects of CRVO were weakened when ML385 was used.</p><p><strong>Conclusions: </strong>In summary, by regulating the Nrf2 pathway, inhalation of CRVO can reduce oxidative stress in depressed mice, thereby reducing neuronal damage and mitochondrial dysfunction to alleviate depression-like behaviours. Our study offers a prospective research foundation to meet the diversity of clinical medication.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627030","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":"Exploring the combined therapeutic efficacy of bexarotene and icariin in type 2 diabetic rats.","authors":"Burak Dik, Tugba Melike Parlak, Mehmet Burak Ates, Oznur Tufan","doi":"10.1093/jpp/rgae100","DOIUrl":"10.1093/jpp/rgae100","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study was to determine the single and combined antidiabetic activity and side effects of the retinoid X receptor agonist bexarotene and the thioredoxin-interacting protein inhibitor and peroxisome proliferator-activated receptor γ and AMP-activated protein kinase activator icariin.</p><p><strong>Methods: </strong>The rats were grouped as healthy (control), diabetes, diabetes + bexarotene (20 mg/kg), diabetes + icariin (60 mg/kg), diabetes + bexarotene (10 mg/kg) + icariin (30 mg/kg) low-dose combination and diabetes + bexarotene (20 mg/kg) + icariin (60 mg/kg) high-dose combination groups.</p><p><strong>Key findings: </strong>Icariin treatment led to a significant reduction in glucose levels compared with the diabetes control group, a remarkable outcome observed 45 days after the initial application. HbA1c levels of the icariin and low-dose combination treatment groups were significantly lower than in the diabetes group. Notably, icariin treatment also significantly elevated HOMA-β levels, which is indicative of improved β-cell function. Icariin significantly decreased glucose levels at 30 and 120 min in the oral glucose tolerance test. Moreover, it ameliorated hepatocyte degeneration, hepatic cord dissociation, congestion, mononuclear cell infiltration in the liver, and degeneration in the pancreas.</p><p><strong>Conclusions: </strong>Icariin treatment exhibited robust antidiabetic effects with fewer side effects than other treatment options in this study. In future studies, long-term and varying doses of icariin will contribute to the development of novel antidiabetic drugs.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723803","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":"Ligusticum chuanxiong Hort.: a review of its phytochemistry, pharmacology, and toxicology.","authors":"Qinghe Kong, Yingshuo Niu, Hao Feng, Xiaofei Yu, Bingkang Wang, Xue Liu, Yueru Chen, Fulin Wang, Jingzhen Tian, Honglei Zhou","doi":"10.1093/jpp/rgae105","DOIUrl":"10.1093/jpp/rgae105","url":null,"abstract":"<p><strong>Background: </strong>Conioselinum anthriscoides (H. Boissieu) Pimenov & Kljuykov, also known as Ligusticum chuanxiong Hort. is a perennial Umbelliferae herb, whose dried rhizome commonly called Chuanxiong Rhizoma. Chuanxiong Rhizoma is widely used in TCM, especially for cardiocerebrovascular and gynecological diseases. However, these studies are scattered and there is no review that can centralize the results of these studies. The authors summarized this review by collecting research results on the chemical, pharmacological, and toxicological of Chuanxiong Rhizoma published in various publications over the past 20 years.</p><p><strong>Aims: </strong>The purpose of this review is to summarize the current experimental studies on Chuanxiong Rhizoma and explore its mechanism of action.</p><p><strong>Methods: </strong>Web of Science, PubMed, CBM, CNKI, Medline, Embase, Elsevier, Springer, Wiley Online Library, Scholar, and other databases were searched, and nearly one hundred experimental studies were collected to summarize this review.</p><p><strong>Results and discussion: </strong>Chuanxiong Rhizoma is composed of essential oil, terpenes, alkaloids, polysaccharide, organic acids, ceramides, and cerebrosides. It has the functions of promoting blood circulation, removing blood stasis, antibacterial, antiviral, and calming the mind to sleep. Now it can be used to treat cardiocerebrovascular and gynecological diseases, neurodegenerative disease, psoriasis, rectal cancer, osteoporosis, and osteoarthritis.</p><p><strong>Conclusions: </strong>In the past 20 years, a large number of research data have confirmed that Chuanxiong Rhizoma contains rich effective metabolites, has huge medicinal potential, and has a wide range of effective treatments.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046815","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":"Melatonin alleviates high glucose-induced cardiomyocyte injury through suppressing mitochondrial FUNDC1-DRP1 axis.","authors":"Junyi Zheng, Lili Zhao, Yingying Zhang, Wenbin He, Xukun Guo, Jixiang Wang","doi":"10.1093/jpp/rgae114","DOIUrl":"10.1093/jpp/rgae114","url":null,"abstract":"<p><strong>Objectives: </strong>To use H9c2 cardiomyocytes to establish a diabetic cardiomyopathic model by exposing these cells to high glucose (HG), followed by treating them with melatonin (MEL) or plasmid vectors overexpressing FUN14 Domain Containing 1 (FUNDC1).</p><p><strong>Methods: </strong>We employed quantitative real-time PCR, mitochondrial staining, and biochemical assays to measure the activity of various antioxidant and mitochondrial complex functions under various treatment conditions.</p><p><strong>Key findings: </strong>Our results showed that HG induced the expression of FUNDC1 and increased mitochondrial oxidative stress and fragmentation, while MEL treatment reversed most of these pathological effects. Moreover, HG exposure activated dynamin-related protein 1 expression and its translocation to mitochondria. Modulation of AMP-activated protein kinase level was found to be another pathological hallmark. In silico molecular docking, analysis revealed that MEL could directly bind the catalytic groove of FUNDC1 through Van der Waal's force and hydrogen bonding. Finally, MEL ameliorated diabetic cardiomyopathy-induced mitochondrial injury through FUNDC1 in vivo.</p><p><strong>Conclusions: </strong>Hyperglycemia induced mitochondrial fragmentation and altered electron transport chain complex functions, which could be ameliorated by MEL treatment, suggesting its potential as a cardiovascular therapeutic.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289724","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":"Unraveling molecular and clinical aspects of ALKBH5 as dual role in colorectal cancer.","authors":"Furqan Memon, Momina Nadeem, Muhammad Sulaiman, Mudassar Iqbal Arain, Umm-E- Hani, Shengtao Yuan","doi":"10.1093/jpp/rgae108","DOIUrl":"10.1093/jpp/rgae108","url":null,"abstract":"<p><strong>Objectives: </strong>This study investigates the dual role of ALKBH5, an eraser enzyme, in colorectal cancer (CRC), focusing on how N6-methyladenosine (m6A) mutations influence CRC development and progression.</p><p><strong>Methods: </strong>We reviewed various studies that highlighted the role of ALKBH5 in colorectal cancer (CRC). This includes the impact of ALKBH5 on tumor cell behavior including immune system interactions, invasion, and proliferation in CRC. We also looked into how ALKBH5 acts as a tumor suppressor under different conditions analyzed clinical data to assess the impact of ALKBH5 expression on outcomes in colorectal cancer patients.</p><p><strong>Key findings: </strong>In CRC, ALKBH5 plays a dual role. In certain situations, it inhibits the progression of the tumor, but in other circumstances, it promotes tumor growth and immunosuppression. The interaction with RABA5 plays a role in the development of CRC. Having elevated levels of ALKBH5 has been associated with unfavorable patient outcomes, such as reduced survival rates and more advanced cancer stages. Various factors, including tumor differentiation, TNM stages, and carcinoembryonic antigen (CEA) levels, be linked to ALKBH5 expression.</p><p><strong>Conclusions: </strong>ALKBH5 plays a complicated and situation-specific role in colorectal cancer (CRC). Targeting ALKBH5 could result in novel therapy options that balance its tumor-promoting and tumor-fighting properties in CRC. Further research into m6A alterations and ALKBH5 could enhance CRC treatment approaches and patient outcomes.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348963","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}