Journal of Advanced Pharmaceutical Technology & Research最新文献

{"title":"Genetic polymorphism and immunological evaluation of PD-1 in Iraqi patients with acute myeloid leukemia.","authors":"Aseel S Mahmood","doi":"10.4103/JAPTR.JAPTR_107_24","DOIUrl":"https://doi.org/10.4103/JAPTR.JAPTR_107_24","url":null,"abstract":"<p><p>PD-1 has a noteworthy function in developing acute myeloid leukemia (AML). The expression of PD-1 on effector T cells is regulated at the protein level depending on the interactions between cells. The objective of the study was to evaluate the PD-1 concentration levels and the polymorphism genetic variants (rs36084323 G/A) in Iraqi Arab patients with AML. Sanger's DNA sequencing was used, and the assessments were done by enzyme-linked immunosorbent assay and PD-1 gene polymorphism SNP rs36084323 G/A. The frequency of rs36084323 was significantly different between AML and control, with a lower risk for AML seen in patients with GA genotype (odds ratio; 95% confidence interval: 0.53; 0.32-0.87). PD-1 elevated AML compared to control (213.1 pg/mL vs. 178.8 pg/mL). in AML patients, there is upregulation in PD-1, which indicates that PD-1 is a possible biomarker for AML. PD-1 rs36084323 G/A may have a role in AML risk.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"15 3","pages":"225-230"},"PeriodicalIF":1.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene polymorphism impact on opioid analgesic usage.","authors":"Sry Suryani Widjaja, Muhammad Ichwan, Balram Chowbay, Rusdiana, Tengku Helvi Mardani, Vito Filbert Jayalie","doi":"10.4103/JAPTR.JAPTR_69_24","DOIUrl":"https://doi.org/10.4103/JAPTR.JAPTR_69_24","url":null,"abstract":"<p><p>Acute pain, moderate-to-severe cancer pain, and persistent malignant pain are all frequently treated with opioids. It is regarded as one of the main tenets of analgesic treatment. The relationship between human opioid sensitivity and genetic polymorphism differences has received little attention up to this point in research. Nonetheless, there is mounting proof that pharmacogenomic diversity could affect how each person reacts to opioids. Finding out how gene polymorphism affects analgesic use is the aim of this investigation, particularly opioids. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards were followed in the preparation of the systematic review approach used in this work. Oxycodone, fentanyl, raclopride, tramadol, ketorolac, morphine, ropivacaine, levobupivacaine, subfentanyl, remifentanil, and nortriptyline were the opioid medications used in the study, which was based on 13 publications. From those articles, we reviewed the impact of gene polymorphism on pain management and drug pharmacokinetics. Based on this systematic review, we concluded that gene polymorphism of gene affects analgesic, specifically opioid mechanisms.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"15 3","pages":"135-138"},"PeriodicalIF":1.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic analysis: Therapeutic drug monitoring of metformin and glimepiride on diabetic patients' plasma including genetic polymorphism.","authors":"Areen Ibrahim, Mohanad Odeh, Eyad Mallah, Luay Abu-Qatouseh, Ahmad Abu Awaad, Mohammad I A Ahmad, Amjad Shdifat, Soadad Saleh, Muwafaq Al Hyari, Ibrahim Khadra, Khaled W Omari, Tawfiq Arafat","doi":"10.4103/JAPTR.JAPTR_99_24","DOIUrl":"https://doi.org/10.4103/JAPTR.JAPTR_99_24","url":null,"abstract":"<p><p>Diabetes is a widespread disease that needs to be controlled. Therapeutic monitoring of drugs is very helpful in maintaining desirable doses. To study a correlation between the blood level of metformin (to a lesser extent, glimepiride) and genotyping (mainly the SULT1A1 genotype). Determine drug levels using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) tool. A validated LC-MS/MS method was developed to determine metformin and glimepiride levels in human plasma. DNA extraction was performed using Jena Bioscience's Blood DNA preparation, in which a column kit was used to extract DNA for genetic polymorphism. The investigation was carried out using both medications in type 2 diabetes patients alongside the genetic polymorphism. One hundred and six patients were assessed. The prevalence of homozygosity for SULT1A1 and wild-type CYP2D6 * 4 were 72.6% and 73.6%, respectively. After adjustment for daily intake of metformin, three patients out of five with the highest levels of metformin had no homozygosity (SULT1A1 genotype). Statistically, variables that demonstrated an insignificant correlation with the level of metformin were body mass index (rs (87) = 0.32, <i>P</i> = 0.011) and age (rs (87) =0.26, <i>P</i> = 0.017). The homozygous (SULT1A1 genotype) correlation was moderate (rs (87) =0.21, <i>P</i> = 0.052). According to the findings, patients with the wt/wt CYP2D6 genotype had considerably greater levels of endoxifen than those with the v/v CYP2D6 genotype. The study's results reported a probable correlation between the blood level of metformin (to a lesser extent, glimepiride) and genotyping (mainly the SULT1A1 genotype). Genotype-guided drug therapy may provide a novel contribution to maximize drug efficacy and/or minimize toxicity.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"15 3","pages":"150-155"},"PeriodicalIF":1.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucomannan is a promising isoniazid's enhancer that inducing macrophage phagocytosis.","authors":"Bernadette Dian Novita, Widya Wasiyastuti, Yudy Tjahjono, Hendy Wijaya, Wuryanto Hadinugroho, Sumi Wijaya, Lisa Soegianto, Imelda Theodora, Elisabeth Tri Wahyuni Widoretno, Kevin Samsudin, Alvin Julian","doi":"10.4103/japtr.japtr_96_24","DOIUrl":"https://doi.org/10.4103/japtr.japtr_96_24","url":null,"abstract":"<p><p>Isoniazid (INH) is a frontline antituberculosis agent effective against <i>Mycobacterium tuberculosis</i> (Mtb), but the increasing challenge of avoiding multidrug-resistant tuberculosis, including INH resistance, necessitates innovative approaches. This study focused on enhancing macrophage phagocytosis to overcome INH resistance. Glucomannan, an immunomodulatory polysaccharide, emerged as a potential macrophage activator. Our objective was to characterize the glucomannan-INH mixture and assess its impact on INH efficacy and macrophage activity. Detailed examination of the glucomannan from <i>Amorphophallus muelleri</i> (0.05%-0.2%) was performed in several methods. INH sensitivity tests were carried out with the Mtb strain H37RV on Löwenstein-Jensen medium. Murine macrophage (RAW264.7) viability and activity were evaluated through MTT and latex bead phagocytosis assays. Ultraviolet-wavelength spectrophotometry was used to analyze chemical structure changes. Glucomannan (0.05%-0.2%) significantly enhanced murine macrophage viability and activity. When glucomannan was combined with INH, the IC50 value was greater compared to INH only. Phagocytosis assays revealed heightened macrophage activity in the presence of 0.05% and 0.1% glucomannan. Importantly, glucomannan did not compromise INH efficacy or alter its chemical structure. This study underscores the potential of glucomannan, particularly with a lower molecular weight, as a promising enhancer of INH, boosting macrophage phagocytosis against INH-resistant Mtb. These findings challenge the assumptions about the impact of glucomannan on drug absorption and prompt potential reevaluation. While specific receptors for glucomannan in macrophage phagocytosis require further exploration, the complement receptors are proposed to be potential mediators.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"15 3","pages":"237-241"},"PeriodicalIF":1.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nephroprotective effect of sugarcane (<i>Saccharum officinarum</i> L.) leaves ethanol extract on gentamicin-induced nephrotoxicity in rats.","authors":"Ika Puspita Dewi, Merinda Aldiana, Zildjian Adela Viadina, Fifteen Aprila Fajrin, Diana Holidah, Fransiska Maria Christianty","doi":"10.4103/JAPTR.JAPTR_440_23","DOIUrl":"https://doi.org/10.4103/JAPTR.JAPTR_440_23","url":null,"abstract":"<p><p>Kidney damage is commonly attributed to using certain drugs, such as gentamicin, which causes elevated kidney parameters in blood and damage to renal tissue. This damage is often a result of oxidative stress, but it can be mitigated by using antioxidants. Several studies proved the potential of sugarcane (<i>Saccharum</i> <i>officinarum</i> L.) leaves as an antioxidant. Therefore, this experiment aimed to examine the nephroprotective action of sugarcane leaves. Twenty-five Wistar rats were separated into the normal, negative, and sugarcane leaf extract (SLE) (200, 400, and 600 mg/kg BW) groups. The animals were handled for 8 days, and then, the blood and tissue were collected 24 h later. The results revealed that SLE prevents increased creatinine, blood urea nitrogen, uric acid, and malondialdehyde levels. The histology analysis indicated that the extract improved kidney morphology and histopathology. Sugarcane leaves have the potential to be a nephroprotective agent.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"15 3","pages":"208-213"},"PeriodicalIF":1.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of <i>Moringa oleifera</i> irrigation solution on the cell metabolism change of <i>Streptococcus mutans</i>.","authors":"Cut Soraya, Fitri Yunita Batubara, Saskia L Nasroen, Subhaini Jakfar, Basri A Gani","doi":"10.4103/JAPTR.JAPTR_442_23","DOIUrl":"https://doi.org/10.4103/JAPTR.JAPTR_442_23","url":null,"abstract":"<p><p>The principal etiological agent responsible for dental caries is <i>Streptococcus mutans</i> <i>(S. mutans</i>). The <i>Moringa oleifera</i> (<i>M. oleifera</i>) possesses antioxidant and antibacterial properties that function through the response to oxidative stress, which affects bacterial cell metabolism. This research examined <i>M. oleifera</i> impact on <i>S. mutans</i> growth, toxicity, glucan-binding protein (GBP) expression, and nucleic acid structure. Methods included spectrophotometry for growth analysis, enzyme-linked immunosorbent assay for GBP quantification, the (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) MTT assay for cytotoxicity, Fourier transform infrared for nucleic acid changes, and docking simulation for ligand-receptor affinity. Results showed that <i>M. oleifera</i> significantly inhibited <i>S. mutans</i> growth at all concentrations over 24 and 48 h (optical density <0.1), comparable to <300 CFU/mL. At 72 h, 6.25% and 3.125% concentrations were most effective, with chlorhexidine also showing stability at these times. A 3.125% concentration of <i>M. oleifera</i> notably reduced GBP production to below 15% and caused cell toxicity. Furthermore, 25% and 3.125% concentrations significantly altered <i>S. mutans</i> nucleic acids, and <i>M. oleifera</i> showed high binding affinity to the GBP gene receptor. Thus, <i>M. oleifera</i> can inhibit <i>S. mutans</i> growth and GBP production, cause nucleic acid deformation, and strongly bind to the GBP receptor, highlighting its potential in dental caries prevention.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"15 3","pages":"200-207"},"PeriodicalIF":1.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the methanol extract of BaiYangJie: Toxicology and protective effect against acute kidney injury.","authors":"Jiaxin Li, Lingjuan Zhou, Jinhui Wang, Lixia Zhang, Bin Xia, Guang Li, Jiahui Ren, Jiacheng Li","doi":"10.4103/JAPTR.JAPTR_467_23","DOIUrl":"https://doi.org/10.4103/JAPTR.JAPTR_467_23","url":null,"abstract":"<p><p>BaiYangJie (BYJ) is a terrestrial perennial plant commonly used as a Dai medicine and has therapeutic effects on liver and kidney diseases. Cisplatin (CP), a chemotherapy drug, has good therapeutic effects but causes many side effects, including nephrotoxicity. This article investigated the toxicology of the methanol extract of BYJ (ME-BYJ) and its protective effect on CP-induced acute kidney injury (AKI) through pharmacological experiments. The results showed that the treated mice had no toxicological symptoms and no anatomical, physiological, or histological abnormalities. The BYJ-high-dose group showed significantly attenuated CP-induced AKI. It is concluded that ME-BYJ has the most significant protective effect on AKI at a dose of 8 g/kg and BYJ was not toxic.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"15 3","pages":"185-193"},"PeriodicalIF":1.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the antioxidant potential of <i>Moringa oleifera</i> leaf extracts mitigating doxorubicin-induced cardiotoxicity in male rats.","authors":"Ruaa Ali Obeid, Rusul Ahmed Mohammed, Raad A Kaskoos, Amira Zair","doi":"10.4103/JAPTR.JAPTR_531_23","DOIUrl":"https://doi.org/10.4103/JAPTR.JAPTR_531_23","url":null,"abstract":"<p><p>Doxorubicin (DOX) is a commonly used drug in chemotherapy for cancer treatment. However, it can cause the threatening side effect of cardiotoxicity. This study investigates whether the hydro-alcoholic leaves of <i>Moringa oleifera</i> have any protective potential against DOX-induced cardiotoxicity. The phytochemical analysis showed that the plant extracts contained bioactive compounds with antioxidant activities. The DOX-treated group confirmed a significant increment in cardiac troponin I (cTnI) and proinflammatory cytokine interleukin-6 (IL-6) levels, which indicates damage to the cardiomyocytes and also inflammation. However, treatment with the <i>M. oleifera</i> extracts significantly inhibited DOX-induced cardiomyocyte damage, as indicated by the significantly low cTnI release. Furthermore, treatment with <i>M. oleifera</i> extracts further increased antioxidant activities, thereby decreasing oxidative stress and lipid peroxidation. Moreover, DOX was found to increase the IL-6 level, and treatment with <i>M. oleifera</i> extracts had a significant impact on the inhibition of IL-6 levels. These results indicate that the <i>M. oleifera</i> extracts have a cardioprotective effect and can play a role as an adjunct drug in mitigating DOX-induced cardiotoxicity, thus providing new prospects for the improvement of safety and efficacy in the treatment of cancer.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"15 3","pages":"166-170"},"PeriodicalIF":1.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of subclinical hypothyroidism in type II diabetes mellitus patients on biochemical, coagulation, and fibrinolysis status.","authors":"Yasir Abbas Atia, Suhad Taha Mohammed, Sarmad S Abdullah, Ahmed Saad Abbas, Hayder Adnan Fawzi","doi":"10.4103/JAPTR.JAPTR_89_24","DOIUrl":"10.4103/JAPTR.JAPTR_89_24","url":null,"abstract":"<p><p>The aim of the currnet study to examine the effect of subclinical hypothyroidism (SCH) in diabetic patients on coagulation parameters. This retrospective case-control study involves 130 patients diagnosed with type 2 diabetes mellitus (T2DM), divided into 65 T2DM with newly diagnosed SCH and 65 euthyroid (EUT) T2DM patients without SCH. Fibrinogen (FIB) was significantly higher in SCH (508.2 ± 63.0 mg/dL) than EUT (428.1 ± 44.8 mg/dL). In the SCH patients, FIB correlated with several parameters, such as age (β = 0.396), body mass index (β = 0.578), glycated hemoglobin (β = 0.281), and activated partial thromboplastin time (β = 0.276). In conclusion SCH in DM patients appears to increase the magnitude of coagulopathy.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"15 2","pages":"130-134"},"PeriodicalIF":1.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant potential and polyphenol content in different parts of <i>Graptophyllum pictum</i> extracts.","authors":"Feda Anisah Makkiyah, Eldiza Puji Rahmi, Rini Anggi Arista, Nelly Marliani, Waras Nurcholis","doi":"10.4103/japtr.japtr_325_23","DOIUrl":"10.4103/japtr.japtr_325_23","url":null,"abstract":"<p><p>The antioxidant potential of <i>Graptophyllum pictum</i> (wungu leaves), an indigenous shrub plant extensively used in traditional medicine in Indonesia, was investigated in this study. The research focused on a comprehensive evaluation of total phenolic content (TPC), total flavonoid content (TFC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric-reducing antioxidant power (FRAP) across various plant parts, including roots, stems, and flowers, which had been underexplored in prior studies. The ethanol extract derived from wungu flowers and leaves demonstrated notable antioxidant potential, characterized by elevated TPC (12.22 ± 0.31 mg GAE/g DW) and FRAP (37.73 ± 1.08 μmol TEAC/g DW) in the ethanol extract of wungu flowers. Similarly, the ethanol extract of wungu leaves showcased a substantial TFC (2.31 ± 0.18 mg QE/g DW) and DPPH (1.12 ± 0.05 μmol TEAC/g DW), surpassing other parts of the wungu plant in the same or different extracts. These findings suggested that ethanol extracts were a promising foundation for herbal medicines with antioxidant properties, highlighting their potential applications in plant breeding programs. Furthermore, the correlation data underscored the significance of the ethyl acetate and ethanol extracts, revealing a robust correlation between TPC, TFC, and FRAP compared to the <i>n</i>-hexane extract.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"15 2","pages":"111-116"},"PeriodicalIF":1.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141433762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}