Cardiovascular & hematological disorders drug targets最新文献

{"title":"Acute Myeloid Leukemia Presenting as Extensive Arterial and Venous Thrombosis: A Case Report.","authors":"Arjun Kachhwaha, Bibhant Shah, Kavya Ronanki, Prisla Maria Dalton, Uttam Kumar Nath","doi":"10.2174/011871529X334859241016114027","DOIUrl":"https://doi.org/10.2174/011871529X334859241016114027","url":null,"abstract":"<p><strong>Background: </strong>Thromboembolism with solid malignancies is a commonly associated feature, which is less common in hematological malignancies. Disseminated intravascular coagulation (DIC) causing thrombotic events is characteristically associated with certain hematological malignancies (e.g., acute promyelocytic leukemia (APL). Acute myeloid leukemia (AML) presenting as extensive thromboembolism is not a common clinical presentation. Anticoagulation in these subsets of patients remains a major challenge since patients often have thrombocytopenia and bleeding manifestations, requiring close monitoring.</p><p><strong>Case presentation: </strong>A 54-year-old male with a known case of ischemic heart disease on regular anti- platelet therapy presented with acute onset progressive shortness of breath with mild anemia. On further evaluation, the patient was diagnosed with bilateral pulmonary artery and venous thrombosis along with left complete renal and partial inferior vena cava (IVC) thrombosis. The patient was started safely on anticoagulant therapy with normal platelet counts. Later, peripheral smear and immunophenotyping by flow cytometry revealed the diagnosis of acute myeloid leukemia, and the patient started its treatment.</p><p><strong>Conclusion: </strong>Extensive arterial and venous thrombosis at presentation of acute myeloid leukemia is an uncommon finding and needs anticoagulation therapy along with the treatment of the underlying disease. Close monitoring of bleeding and maintaining an adequate platelet count is required, especially in hematological malignancies.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inter-atrial Septum Stenting in Congenital Heart Disease Patient: A Case Series in Indonesia.","authors":"Radityo Prakoso, Yovi Kurniawati, Sisca Natalia Siagian, Aditya Agita Sembiring, Damba Dwisepto Aulia Sakti, Brian Mendel, Olfi Lelya, Oktavia Lilyasari","doi":"10.2174/011871529X320825240925073605","DOIUrl":"https://doi.org/10.2174/011871529X320825240925073605","url":null,"abstract":"<p><strong>Background: </strong>Inter-atrial septum (IAS) stenting in duct-dependent congenital heart disease patient has shown to be an effective way to maintain inter-atrial blood flow, however it is still considered a high risk procedure and inter-atrial septum stenting remains a low-frequency procedure.</p><p><strong>Method: </strong>A single-center observational cohort study was carried out at the National Cardiovascular Center Harapan Kita (NCCHK) between April 2019 and April 2023. This study included duct-dependent congenital heart disease patients. The extracted data were baseline characteristics, clinical findings, complications, and outcomes of the patients.</p><p><strong>Result: </strong>Eleven patients with duct-dependent physiology were intervened with inter-atrial septum stenting. The patients were 4 females and 7 males with the median age of implantation being 150 days (range 11-703 days) and the median weight being 3.9 (range 2.8-9) kg, with 2 patients weighing less than 3 kg. The average stent diameter was 8.50 (2.03) mm with an average length of 24.45 (7.94) mm. Non-restrictive atrial flow was successfully achieved in 90.90% of the procedures, corresponding to 10 patients.</p><p><strong>Conclusion: </strong>Inter-atrial septum stenting in duct-dependent congenital heart disease patients produces reliable patency with a very good intra-procedural success rate.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Role of Secondary Metabolites from Plants and Microbes as Modulators of Macrophage Differentiation.","authors":"Prakhar Sharma, Modi Kiran Piyushbhai, Kaliyamurthi Venkatachalam, Ambika Binesh","doi":"10.2174/011871529X327064241003072202","DOIUrl":"https://doi.org/10.2174/011871529X327064241003072202","url":null,"abstract":"<p><p>Recent research has uncovered that secondary metabolites-biologically active compounds produced by plants, microbes, and other organisms-play a significant role in regulating the differentiation and function of macrophages. Macrophages, key components of the innate immune system, are crucial for a wide range of physiological processes, including immune response modulation, tissue homeostasis, and host defense against pathogens. This research delves into the mechanisms by which secondary metabolites influence macrophage differentiation signaling pathways, with a focus on how specific compounds affect macrophage polarization and functional phenotypes. Understanding these effects can open new avenues for developing therapeutic strategies that target macrophage-mediated immune responses. Secondary metabolites, such as nitrogen (N) and sulfur (S) containing compounds, terpenoids, and phenolic compounds from plants and microbes, can modulate macrophage differentiation by influencing cytokine production and activity. The activation of signaling pathways in macrophages involves multiple receptors and transcription factors, including IFN-γ receptor activation leading to STAT1 activation, TLR4 triggering IRF5, NFκB, and AP1, IL-4 receptor activation leading to STAT6 and IRF4 activation, PPARγ activation via the fatty acid receptor, TLR4 increasing CREB and C/EBP levels. The complex interplay between transcription factors and cytokines is crucial for maintaining the balance between the M1 and M2 states of macrophages. Despite these insights, further research is needed to unravel the specific molecular mechanisms involved and to identify promising secondary metabolites that could be translated into clinical applications.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dengue Fever Related Reactive Thrombocytosis in Young Male: A Case Report and Review Literature.","authors":"Jitendra Singh, Anju Dinkar, Nilesh Kumar, Kailash Kumar, Vikrant","doi":"10.2174/011871529X325967240916075554","DOIUrl":"https://doi.org/10.2174/011871529X325967240916075554","url":null,"abstract":"<p><strong>Introduction: </strong>Dengue fever is prevalent in tropical nations, especially India. Leucopenia and thrombocytopenia are distinctive features of acute dengue fever that revert to normal levels after the patient's recovery. Dengue fever is associated with numerous unusual clinical manifestations of different body systems. Additionally, the emergence of severe thrombocytosis following thrombocytopenia is extremely rare. Based on our extensive knowledge, only three cases similar to this have been documented in the literature.</p><p><strong>Case report: </strong>Here, we present a case of a 36-year-old healthy man who had acute dengue and subsequently developed severe reactive thrombocytosis. The patient was treated conservatively and discharged. Subsequently, he developed thrombocytosis. Aspirin was given for a short period to alleviate any potential repercussions.</p><p><strong>Conclusion: </strong>Thrombocytosis, a rare consequence of dengue infection, is usually asymptomatic. Nevertheless, ongoing monitoring of dengue patients is required to avoid complications.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toll-like Receptors: Therapeutic Potential in Life Threatening Diseases-Cardiac Disorders.","authors":"Sonia Singh","doi":"10.2174/011871529X348433240915133309","DOIUrl":"https://doi.org/10.2174/011871529X348433240915133309","url":null,"abstract":"<p><p>Toll-like receptors (TLRs) belong to the innate immune system. TLRs identify and respond to invading pathogens by recognizing certain molecular patterns associated with the infections. TLRs are crucial for the host's defence against these diseases. TLRs are capable of detecting several endogenous chemicals through the recognition of damage-associated molecular patterns, which are generated in response to various harmful situations. Recent animal studies have shown that TLR signaling has a significant role in the development of serious heart diseases, such as ischemia myocardial damage, myocarditis, and septic cardiomyopathy, where inflammation of the heart muscle is a key factor. This manuscript examines the animal research findings on (1) TLRs, TLR ligands, and the signal transduction system, and (2) the significant involvement of TLR signaling in these crucial cardiac diseases.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding Interactions between a Potential Antimalarial 'MAL2-11B' and its Targets using In Silico Methods.","authors":"Komalpreet Kaur Sandhu, Satinder Kaur, Rachna Hora, Prakash Chandra Mishra","doi":"10.2174/011871529X309936240821072630","DOIUrl":"https://doi.org/10.2174/011871529X309936240821072630","url":null,"abstract":"<p><strong>Introduction: </strong>The 70 kDa heat shock proteins (Hsp70) are ubiquitous molecules that play central roles in protein homeostasis. Their nucleotide-binding domains (NBD) are associated with the J domains of 40 kDa co-chaperone 'HSP40' in performing their functions. Interruption of this interaction significantly impacts the critical ATPase activity of Hsp70s, making them dysfunctional.</p><p><strong>Methods: </strong>MAL2-11B is a dihydropyrimidine derivative that blocks Hsp70-Hsp40 interaction and hence holds the potential to be used as a drug. This Hsp70 inhibitor is a structural analogue of MAL3-101 that has proven anti-cancer and antiparasitic activity. MAL2-11B is predicted to have better drug-likeness, solubility, and absorption properties than MAL3-101. In the present study, we have therefore explored the potential of MAL2-11B as an antimalarial by using in silico tools.</p><p><strong>Results: </strong>Molecular docking of MAL2-11B with all Plasmodium falciparum Hsp70 (PfHsp70) proteins revealed its preferential affinity for two out of four homologs at the nucleotide-binding site. Detailed analysis of the docked complexes helped us to predict the kind of protein-inhibitor interactions and specific amino acid residues involved in binding.</p><p><strong>Conclusion: </strong>After in vitro validation, these data may be used as the groundwork for the design and development of new inhibitors and drugs against malaria.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Misdiagnosed Isolated Ruptured Mycotic Mitral Valve Aneurysm as Mitral Annulus Calcification.","authors":"Sara Afshar, Mohsen Moohebati, Mehdi Kahrom, Kianmehr Rastgou, Mehrdad Hashemi, Vafa Baradaran Rahimi","doi":"10.2174/011871529X313367240722040919","DOIUrl":"https://doi.org/10.2174/011871529X313367240722040919","url":null,"abstract":"<p><strong>Introduction: </strong>Subacute Bacterial Endocarditis (SBE) is a slowly developing type of infective endocarditis. Aneurysm is more common in this type of endocarditis. Currently, SBE is an uncommon cause of unexplained fever (FUO) because rapid diagnostic capabilities, such as echocardiography, have improved. Despite echocardiography, endocarditis and valvular aneurysm were missed in our patient due to the location and special shape of the aneurysm near the annulus.</p><p><strong>Case representation: </strong>We present a case of SBE resulting in an isolated ruptured mycotic mitral valve aneurysm in a patient on dialysis. Mycotic mitral valve aneurysm is an uncommon and serious complication of infective endocarditis, particularly subacute endocarditis.</p><p><strong>Conclusion: </strong>In order to diagnose this complication, there should be clinical suspicion in the presence of severe regurgitation without any cause, and a detailed echocardiography should be performed.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Antihypertensive Potential of Aqueous extract of Peristrophe Bivalvis (L.) Merr. is via Up-regulation of Cyclic Guanosine Monophosphate and Down-regulation of the Renin-angiotensin System.","authors":"Esther Oluwasola Aluko, Ubong Edem David, Abodunrin Adebayo Ojetola, Adesoji Adedipe Fasanmade","doi":"10.2174/011871529X301799240715091918","DOIUrl":"https://doi.org/10.2174/011871529X301799240715091918","url":null,"abstract":"<p><strong>Background: </strong>Hypertension is a major risk factor for cardiovascular diseases. Peristrophe bivalvis (PB) is used for the treatment of hypertension, painful sprains, skin diseases, tuberculosis, acute bronchitis, anti-inflammatory conditions, hepatitis, and diabetes. Its antihypertensive potential has been investigated and documented. This study investigated the antihypertensive mechanism of aqueous extract of PB leaf (APB) on L-NAME-induced hypertension.</p><p><strong>Methods: </strong>Thirty male wistar rats (150-170 g) were grouped into five (n=5). Group 1 received 10 mL/kg of distilled water (control), while groups 2-5 were administered 60 mg/kg of L-NAME (L-- NAME60) orally for eight weeks to induce hypertension. After eight weeks, groups 2-5 received L-NAME60+distilled water (HNT), distilled water (HRE), L-NAME60+APB (200 mg/kg, [HAPB]), and L-NAME60+ramipril (10 mg/kg, [HRA]), respectively, for five weeks. The BP was measured by the tail-cuff method. The blood sample was obtained under anesthesia, and tissue samples were obtained after euthanasia. Serum renin, ACE, angiotensin-II, endothelin-1, and cyclic guanosine monophosphate (cGMP) levels were measured using ELISA techniques. Malondialdehyde, superoxide dismutase (SOD), and reduced glutathione (GSH) levels were measured by spectrophotometry. Data were analyzed using ANOVA at α0.05.</p><p><strong>Results: </strong>The BP significantly decreased in HAPB compared to HNT. Renin, ACE, and angiotensin-II levels significantly decreased while cGMP levels increased in the HAPB group compared to HNT. Malondialdehyde levels significantly decreased, and SOD and GSH levels increased compared to HNT.</p><p><strong>Conclusion: </strong>Peristrophe bivalvis aqueous leaf extract reduced blood pressure in hypertensive rats by modulating the cGMP signalling pathway and the renin-angiotensin system.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immediate Destiny of Bifurcation Lesions Treated with Biomatrix Alpha Stents.","authors":"Mahdi Zahedi, Mohammad Javad Najafi, Mina Sadeghi, Alireza Fatemi","doi":"10.2174/011871529X313209240708073302","DOIUrl":"https://doi.org/10.2174/011871529X313209240708073302","url":null,"abstract":"<p><strong>Background: </strong>About 15% of coronary artery interventions are performed on coronary artery bifurcation. Managing these lesions presents a significant therapeutic obstacle in the context of coronary artery issues. Addressing both immediate and lasting side effects of these lesions demands ongoing monitoring and action. The introduction of drug-eluting stents has raised hopes for better outcomes in patients experiencing cardiovascular events.</p><p><strong>Methods: </strong>In this study, we selected 51 patients (out of 850) who had received ≥1 cobalt-chromium, biodegradable polymer, Biolimus A9-eluting stent (CoCr-BP-BES) Biomatrix Alpha stent. Immediately after stenting, thrombolysis in myocardial infarction (TIMI) flow score in the coronary artery and its bypass branch, plaque shift, and lateral dissection immediately after angioplasty were evaluated.</p><p><strong>Results: </strong>The mean age for patients was 65 (±10.35) years, where 49.02% of them were male and 45.1% had diabetes. No lateral dissection and death were reported in any of the patients. Also, the TIMI flow grade was 3 for the main branch in all patients. Plaque shifts were compared at different degrees of the TIMI flow coronary artery bypass graft. A statistical study revealed a noteworthy distinction between the groups. There was no discernible change when gender, diabetes, systolic and diastolic blood pressure with plaque changes were all controlled for.</p><p><strong>Conclusion: </strong>We discovered that the Biomatrix Alpha stents' instant clinical results are admissible. Our findings confirm the clinical utility of the recently developed biolimus-eluting (BES) stent technology, which combines the BA-9 medication, a thin-strut CoCr stent platform, and a biodegradable polymer. This aligns with the existing body of research on the most recent generation of drug-eluting stents (DES).</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hematological Indices and Genetic Variants of Premature Ovarian Insufficiency: Machine Learning Approaches.","authors":"Mohammad Reza Mirinezhad, Malihe Aghasizadeh, Hamideh Ghazizadeh, Anahid Hemmatpur, Mohammad Reza Fazl Mashhadi, Hamed Khedmatgozar, Amir Kiyoumarsioskouei, Ali Ebrahimi Dabagh, Mohammad Amin Mohammadi, Arezoo Rastegarmoghadam Ebrahimian, Melika Malek, Sara Moazedi, Simin Rashidian, Gordon A Ferns, Tayebeh Hamzehloei, Alireza Pasdar, Majid Ghayour-Mobarhan","doi":"10.2174/011871529X297081240613075328","DOIUrl":"10.2174/011871529X297081240613075328","url":null,"abstract":"<p><strong>Background: </strong>Premature Ovarian Insufficiency (POI) is associated with infertility. Little is known about the potential circulating biomarkers that could be used to predict POI. We have investigated the possible association between white and red blood cells, platelet indices, and eight established single nucleotide polymorphisms (SNPs) associated with POI risk.</p><p><strong>Methods: </strong>117 women with premature menopause (PM) and 183 healthy women without a history of menopause before age 40 were recruited for this study. The tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra ARMS PCR) and allele-specific oligonucleotides- polymerase chain reaction (ASO-PCR) were carried out for genotyping for eight SNPs reported to be associated with POI. Decision tree analysis was applied to test the diagnostic value of hematological parameters to identify the risk of POI.</p><p><strong>Results: </strong>Women with POI had lower neutrophil (NEUT) and white blood cell (WBC), whereas red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), and mean cell hemoglobin (MCH) were higher. Platelet (PLT) count was also lower in affected women. Our data also indicated that HGB and HCT count were significantly associated with rs16991615 and rs244715. Mean Platelet volume (MPV) and platelet distribution width (PDW) were associated with rs244715, rs1046089, rs4806660, and rs2303369. The rs16991615 was also associated with RBC count, and rs451417 was associated with NEUTs. The decision tree (DT) model reveals that women with the NEUT count at a cut-off value of less than 2.8 and HCT equal to or more than 38.7% could be identified as high-risk cases for POI. Overall, we found the DT approach had a sensitivity = 85%, specificity = 72%, and accuracy = 74%.</p><p><strong>Conclusion: </strong>The genetic variants involved in POI are associated with changes in reproductive hormone levels and with changes in hematological indices.</p>","PeriodicalId":93925,"journal":{"name":"Cardiovascular & hematological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}