American Journal of Chinese Medicine最新文献

{"title":"Pharmacological Benefits and Underlying Mechanisms of <i>Salvia miltiorrhiza</i> against Molecular Pathology of Various Liver Diseases: A Review.","authors":"Cho Hyun Hwang,&nbsp;Eungyeong Jang,&nbsp;Jang-Hoon Lee","doi":"10.1142/S0192415X23500763","DOIUrl":"10.1142/S0192415X23500763","url":null,"abstract":"<p><p><i>Salvia miltiorrhiza</i> Bunge, called Danshen in Chinese, is the dried root and rhizome of <i>S. miltiorrhiza</i>, which is part of the mint family, Lamiaceae; it has chiefly been used to treat blood stasis and improve blood flow in cerebrovascular and cardiovascular diseases for over 2000 years. Recent preclinical studies have indicated that <i>S. miltiorrhiza</i> has a wide range of pharmacological properties making it useful for the treatment of diverse liver diseases. <i>S. miltiorrhiza</i> protects the liver from harmful hepatotoxins, reduces hepatic oxidative stress, ameliorates steatosis, and alleviates hepatic inflammation, fibrosis, and cancer. Moreover, several key mechanisms, including apoptosis, AMP-activated protein kinase, mitogen-activated protein kinase, and nuclear factor kappa B, may be involved in the benefits of <i>S. miltiorrhiza</i> in hepatic disorders. In particular, salvianolic acid B and cryptotanshinone, both compounds derived from <i>S. miltiorrhiza</i>, possess therapeutic activities similar to those of <i>S. miltiorrhiza</i>, and thus may play a crucial role in the therapeutic activity of <i>S. miltiorrhiza</i> in liver diseases. Because reports on the pharmacological effects of this herb are scattered, this review aimed to consolidate the available literature to allow the re-evaluation and identification of gaps to guide future research. This review focuses on the role of <i>S. miltiorrhiza</i> in improving the molecular pathology of liver diseases, as reported in <i>in vitro</i> and <i>in vivo</i> studies.</p>","PeriodicalId":50814,"journal":{"name":"American Journal of Chinese Medicine","volume":" ","pages":"1675-1709"},"PeriodicalIF":5.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10486396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Chinese Medicine on Pyroptosis in Coronary Heart Disease.","authors":"Chuangpeng Li,&nbsp;Qingqing Liu,&nbsp;Qiuxiong Chen,&nbsp;Peizhong Liu,&nbsp;Dawei Wang,&nbsp;Rongyuan Yang,&nbsp;Qing Liu","doi":"10.1142/S0192415X23500751","DOIUrl":"10.1142/S0192415X23500751","url":null,"abstract":"<p><p>Pyroptosis, an apoptotic pathway for pro-inflammatory cells, has attracted attention from researchers because of its role in the development of cardiac inflammation reactions. Chinese medicine (CM) has been given more and more attention during the pursuit of a treatment for coronary heart disease (CHD). Evidence suggests that myocardial cell pyroptosis affects the progression of CHD. Pyroptosis pathways include the canonical pyroptosis pathway mediated by the caspase-1 inflammasome and the non-canonical pyroptosis pathway induced by cytoplasmic lipopolysaccharide-activated caspase-4/5/11. The frequently studied compounds that regulate pyroptosis in CHD include astragaloside IV (AS-IV), tanshinone IIA, aucubin, cinnamaldehyde (CD), ginsenoside Rb1, paeoniflorin, apigenin, berberine (BBR), ruscogenin (Rus), and total glucosides of paeonia (TGP). The patent drugs of CM that regulate pyroptosis in CHD include the Qishen granule (QSG), the Simiao Yong'an decoction (SMYAD), the Buyang Huanwu decoction (BYHWD), and the Shexiang Baoxin pill (SBP). Therefore, this paper reviews the pathogenesis of pyroptosis, the role of pyroptosis in CHD, and the potential therapeutic roles of CMs and their active ingredients targeting cell pyroptosis in the development of CHD.</p>","PeriodicalId":50814,"journal":{"name":"American Journal of Chinese Medicine","volume":" ","pages":"1653-1673"},"PeriodicalIF":5.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10486400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ERRATUM: Quercetin Inhibits Intrahepatic Cholangiocarcinoma by Inducing Ferroptosis and Inhibiting Invasion via the NF-[Formula: see text]B Pathway.","authors":"Yinghui Song,&nbsp;Zhihua Zhang,&nbsp;Qin Chai,&nbsp;He Zheng,&nbsp;Yuchen Qi,&nbsp;Guoyi Xia,&nbsp;Zhangtao Yu,&nbsp;Ranzhiqiang Yang,&nbsp;Junkai Huang,&nbsp;Yuhang Li,&nbsp;Chuang Peng,&nbsp;Bo Jiang,&nbsp;Sulai Liu","doi":"10.1142/S0192415X23920027","DOIUrl":"https://doi.org/10.1142/S0192415X23920027","url":null,"abstract":"","PeriodicalId":50814,"journal":{"name":"American Journal of Chinese Medicine","volume":"51 6","pages":"1613-1614"},"PeriodicalIF":5.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10108360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biometrics Data Visualization of Ginsenosides in Anticancer Investigations.","authors":"Ying Chang,&nbsp;Zhongqi Lu,&nbsp;Jinyuan Sui,&nbsp;Tiefeng Jin,&nbsp;Meihua Zhang","doi":"10.1142/S0192415X23500039","DOIUrl":"https://doi.org/10.1142/S0192415X23500039","url":null,"abstract":"<p><p>Ginsenoside extracts have been shown to have anticancer effects by a growing number of studies and have thus become a hot topic in cancer research. Our study used VOSviewer and CiteSpace softwares to conduct a bibliometric approach to co-citation and co-occurrence analysis of countries, institutions, authors, references, and keywords in the field of cancer research to investigate the current status and trends of ginsenosides research in cancer. The web of science core collection (WoSCC) contained a total of 1102 papers. China made the most contributions in this area, with the most publications (742, 67.3%), and collaborated closely with Korea and the USA. The <i>Journal of Ginseng Research</i>, with the most total citations (1607) and an IF of 6.06, is the leading journal in the field of ginsenoside and cancer research, publishing high quality articles. Saponin and its extracts inhibit oxidative stress, promote apoptosis, and inhibits chemotherapy resistance by ginsenosides, all of which are hot research areas in this field. In the coming years, it is expected that the combination of ginsenosides and nanoparticles, in-depth mechanisms of cancer inhibition, and targeted therapy will receive widespread attention.</p>","PeriodicalId":50814,"journal":{"name":"American Journal of Chinese Medicine","volume":"51 1","pages":"35-51"},"PeriodicalIF":5.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9204314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bergenin Inhibits Tumor Growth and Overcomes Radioresistance by Targeting Aerobic Glycolysis.","authors":"Xiaoying Li,&nbsp;Li Xie,&nbsp;Li Zhou,&nbsp;Yu Gan,&nbsp;Shuangze Han,&nbsp;Yuanfeng Zhou,&nbsp;Xiang Qing,&nbsp;Wei Li","doi":"10.1142/S0192415X23500842","DOIUrl":"10.1142/S0192415X23500842","url":null,"abstract":"<p><p>Hexokinase 2 (HK2), the first glycolytic rate-limiting enzyme, is closely correlated with the occurrence and progression of tumors. Effective therapeutic agents targeting HK2 are urgently needed. Bergenin has exhibited various pharmacological activities, such as antitumor properties. However, the effects of bergenin on the abnormal glucose metabolism of cancer cells are yet unclear. In this study, HK2 was overexpressed in OSCC tissues, and the depletion of HK2 inhibited the growth of OSCC cells <i>in vitro</i> and <i>in vivo</i>. Moreover, these results showed that the natural compound, bergenin, exerted a robust antitumor effect on OSCC cells. Bergenin inhibited cancer cell proliferation, suppressed glycolysis, and induced intrinsic apoptosis in OSCC cells by downregulating HK2. Notably, bergenin restored the antitumor efficacy of irradiation in the radioresistant OSCC cells. A mechanistic study revealed that bergenin upregulated the protein level of phosphatase and the tensin homolog deleted on chromosome 10 (PTEN) by enhancing the interaction between PTEN and ubiquitin-specific protease 13 (USP13) and stabilizing PTEN; this eventually inhibited AKT phosphorylation and HK2 expression. Bergenin was identified as a novel therapeutic agent against glycolysis to inhibit OSCC and overcome radioresistance. Targeting PTEN/AKT/HK2 signaling could be a promising option for clinical OSCC treatment.</p>","PeriodicalId":50814,"journal":{"name":"American Journal of Chinese Medicine","volume":" ","pages":"1905-1925"},"PeriodicalIF":5.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10468286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginseng as a Key Immune Response Modulator in Chinese Medicine: From Antipandemic History to COVID-19 Management.","authors":"Yanyi Liu,&nbsp;Kun Xia,&nbsp;Shixu Liu,&nbsp;Wei Wang,&nbsp;Guangxi Li","doi":"10.1142/S0192415X23500027","DOIUrl":"https://doi.org/10.1142/S0192415X23500027","url":null,"abstract":"<p><p>The cytokine storm plays an indispensable role in the severe and critical illness and death of the COVID-19 vulnerable population. Thus, suppressing the cytokine storm is of great significance. Ginseng is a traditional Chinese herb originally used for improving physiological conditions and ameliorating disease. Common throughout the history of ancient Chinese medicine is utilizing ginseng as a major ingredient to successfully fight various pandemics, and the most famous decoction is Renshen Baidu powder. In recent years, ginseng has been observed to provide preventive and therapeutic benefits in the treatment of various conditions by suppressing hyper-inflammation, inhibiting virus intrusion, and balancing the host's immunity. This paper summarizes the ancient Chinese medicine books' recordings of, the clinical practice of, and the laboratory exploration of ginseng for the treatment of pandemics and COVID-19. Ginseng and its active ingredients were found to downregulate inflammatory cytokines, upregulate anti-inflammatory cytokines, stimulate the secretion of the antiviral cytokine IFN-[Formula: see text], prevent viral entry and replication, and improve viral clearance. Furthermore, ginseng modulates both natural and acquired immunity during viral infection. Collectively, we propose that ginseng can act as a key immune response modulator against the cytokine storm of COVID-19. This paper may provide a new approach to discover specific medications using ginseng to combat COVID-19.</p>","PeriodicalId":50814,"journal":{"name":"American Journal of Chinese Medicine","volume":"51 1","pages":"19-34"},"PeriodicalIF":5.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10637124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects and Mechanistic Role of Mulberry Leaves in Treating Diabetes and its Complications.","authors":"Yanjiao Zhang,&nbsp;Runyu Miao,&nbsp;Kaile Ma,&nbsp;Yuxin Zhang,&nbsp;Xinyi Fang,&nbsp;Jiahua Wei,&nbsp;Ruiyang Yin,&nbsp;Jingxue Zhao,&nbsp;Jiaxing Tian","doi":"10.1142/S0192415X23500775","DOIUrl":"10.1142/S0192415X23500775","url":null,"abstract":"<p><p>Diabetes mellitus (DM) has become a surge burden worldwide owing to its high prevalence and range of associated complications such as coronary artery disease, blindness, stroke, and renal failure. Accordingly, the treatment and management of DM have become a research hotspot. Mulberry leaves (<i>Morus alba</i> L.) have been used in Traditional Chinese Medicine for a long time, with the first record of its use published in Shennong Bencao Jing (Shennong's Classic of Materia Medica). Mulberry leaves (MLs) are considered highly valuable medicinal food homologs that contain polysaccharides, flavonoids, alkaloids, and other bioactive substances. Modern pharmacological studies have shown that MLs have multiple bioactive effects, including hypolipidemic, hypoglycemic, antioxidation, and anti-inflammatory properties, with the ability to protect islet [Formula: see text]-cells, alleviate insulin resistance, and regulate intestinal flora. However, the pharmacological mechanisms of MLs in DM have not been fully elucidated. In this review, we summarize the botanical characterization, traditional use, chemical constituents, pharmacokinetics, and toxicology of MLs, and highlight the mechanisms involved in treating DM and its complications. This review can provide a valuable reference for the further development and utilization of MLs in the prevention and treatment of DM.</p>","PeriodicalId":50814,"journal":{"name":"American Journal of Chinese Medicine","volume":" ","pages":"1711-1749"},"PeriodicalIF":5.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10486401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism and Molecular Targets of a Water-Soluble Extract of <i>Artemisia annua</i> on the Treatment of Alzheimer's Disease Based on Network Pharmacology and Experimental Validation.","authors":"Wen-Shu Zhou,&nbsp;Marta Silva,&nbsp;Chao Yang,&nbsp;Shuai Li,&nbsp;Yi-Tian Chen,&nbsp;Wen-Hua Zheng","doi":"10.1142/S0192415X23500295","DOIUrl":"https://doi.org/10.1142/S0192415X23500295","url":null,"abstract":"<p><p>Oxidative stress is an important contributor to the pathogenesis of Alzheimer's disease (AD). The overproduction of reactive oxygen species observed in AD patients results in the loss of mitochondrial function, altered metal ion homeostasis, lipopolysaccharide metabolism disorder, reduced anti-oxidant defense, increased release of inflammatory factors, and the aggravation and accumulation of amyloid-beta and tau hyper-phosphorylation, which directly cause synaptic and neuronal loss and lead to cognitive dysfunction. Thus, oxidative stress proves to be a fundamental part of AD development and progression, suggesting the potential benefits of anti-oxidant-based therapies for AD. In this study, we found that a water-soluble extract of <i>Artemisia annua</i> (<i>WSEAA</i>), a traditional Chinese herbal medicine, has a strong anti-oxidant function. We also found that <i>WSEAA</i> is able to improve the cognitive function of 3xTg AD mice. However, the mechanisms and molecular targets underlying <i>WSEAA</i> action are still not known. In order to uncover the potential molecular mechanisms involved, we used a combination of network pharmacology and different experimental approaches. Obtained results revealed key genes (such as AKT1, BCL2, IL-6, TNF-[Formula: see text] and BAX) and signaling pathways (like PI3K-AKT and BCL2/BAX) are closely associated with the biological processes responding to oxidative stress. Further verification of the survival/anti-oxidant effects of <i>WSEAA in vitro</i> and <i>in vivo</i> showed that the extract has anti-oxidatant/neuronal survival action against H₂O₂-induced damage, and is thus able to prevent the cognitive decline and pathological changes of 3xTg transgenic (3xTg) mice via the regulation of key target-genes and pathways, such as PI3K-AKT and BCL2/BAX, related to survival/apoptosis. Our findings strongly indicate the potential of <i>WSEAA</i> for the prevention and treatment of AD.</p>","PeriodicalId":50814,"journal":{"name":"American Journal of Chinese Medicine","volume":"51 3","pages":"595-622"},"PeriodicalIF":5.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9596424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Role of <i>Scutellaria baicalensis</i> Georgi in Breast Cancer Therapy.","authors":"Peng Yu,&nbsp;Jingyang Li,&nbsp;Yanqing Luo,&nbsp;Jiayi Sun,&nbsp;Yingfan Hu,&nbsp;Bo Lin,&nbsp;Xianli Meng,&nbsp;Li Xiang","doi":"10.1142/S0192415X23500155","DOIUrl":"https://doi.org/10.1142/S0192415X23500155","url":null,"abstract":"<p><p>Breast cancer is one of the most common malignancies in women, and exhibits high metastasis, recurrence and fatality rates. Novel therapies for breast cancer are constantly emerging, such as targeted therapy, oncolytic virotherapy, and immunotherapy. Despite their potential, these new therapies are still in their infancy, and chemotherapy remains the standard treatment for breast cancer. Therefore, it is of great significance to develop safe and efficient treatment drugs or adjuvants for breast cancer treatment. Traditional Chinese medicine (TCM) has a long clinical history in China, in which <i>Scutellaria baicalensis</i> Georgi exhibits favorable antibreast cancer activities. We therefore conducted a systematic review of the available literature to better understand the molecular mechanisms of <i>S. baicalensis</i> in breast cancer treatment. <i>S. baicalensis</i> and its active components (baicalein, baicalin, wogonin, wogonoside, oroxylin A and scutellarin) exhibited promising antibreast cancer activity through proliferation inhibition, apoptosis induction, invasion and metastasis blockading, and drug-resistance and non-coding RNA regulation. Additionally, senescence, autophagy, angiogenesis, and glycolysis mechanisms were observed to play a role in their antibreast cancer activity. Furthermore, multiple signaling pathways contributed to the antitumor effects of <i>S. baicalensi</i>, such as the NF-[Formula: see text]B, Wnt/[Formula: see text]-catenin, SATB1, Bcl2 family proteins, Caspase, PI3K/Akt, mTOR, ERK, p38-MAPK, TGF-[Formula: see text]/Smad, and Hippo/YAP pathways. This review provides valuable insights into the role of <i>S. baicalensis</i> as a breast cancer treatment and acts as a foundation for further investigations in this field.</p>","PeriodicalId":50814,"journal":{"name":"American Journal of Chinese Medicine","volume":"51 2","pages":"279-308"},"PeriodicalIF":5.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9563100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Glycyrrhizic Acid in Treatment of Autoimmune Hepatitis.","authors":"Xiaoyue Bi,&nbsp;Liu Yang,&nbsp;Yanjie Lin,&nbsp;Wen Deng,&nbsp;Tingting Jiang,&nbsp;Lu Zhang,&nbsp;Yao Lu,&nbsp;Wei Yi,&nbsp;Yao Xie,&nbsp;Minghui Li","doi":"10.1142/S0192415X23500209","DOIUrl":"https://doi.org/10.1142/S0192415X23500209","url":null,"abstract":"To compare the long-term efficacy and safety of glycyrrhizic acid preparation and hormone treatment in patients with autoimmune hepatitis, we enrolled 377 patients in a study that lasted from January 2009 to January 2020. After performing propensity score matching, we included 58 patients in the hormone group and 58 in the glycyrrhizic acid preparation group in statistical analysis. We then compared the ratio of sustained biochemical responses at 48 weeks after treatment. Adverse events, including some incidence of decompensated liver cirrhosis and liver cancer, were evaluated. The results showed that a total of 61.8% of treated patients achieved complete biochemical remission. The cumulative biochemical remission rate in the hormone group and glycyrrhizic acid preparation group showed no significant difference (62.3% vs. 60.7%, [Formula: see text], [Formula: see text]). At the end of follow-up, the total bile acid in the hormone group was significantly higher than that in the glycyrrhizic acid preparation group (8.9[Formula: see text][Formula: see text]mol/L vs. 5.6[Formula: see text][Formula: see text]mol/L, [Formula: see text], [Formula: see text]). The incidence of adverse reactions in the hormone group was significantly higher than that in the glycyrrhizic acid preparation group (31.03% vs. 15.52%, [Formula: see text], [Formula: see text]). In conclusion, compared with the hormone treatment, glycyrrhizic acid preparation might be a safe and effective treatment for autoimmune hepatitis.","PeriodicalId":50814,"journal":{"name":"American Journal of Chinese Medicine","volume":"51 2","pages":"391-405"},"PeriodicalIF":5.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9563101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}