Journal of Advanced Pharmaceutical Technology & Research最新文献

{"title":"Supercritical CO₂ extraction of <i>Clinacanthus nutans</i>: Enhanced bioactive recovery and cytotoxicity against cervical cancer cells.","authors":"Lukkhana Benjawan, Pakaporn Sathalalai, Somnuk Promdaeng, Siriphan Sukkhung, Siriwan Tipparak, Wiriyaporn Sumsakul, Thanvisith Charoenying","doi":"10.4103/JAPTR.JAPTR_101_25","DOIUrl":"10.4103/JAPTR.JAPTR_101_25","url":null,"abstract":"<p><p>This study optimized supercritical CO₂ extraction (SCE) of <i>Clinacanthus nutans</i> leaves, with or without 80:20 ethanol-water co-solvent (CoS), and benchmarked it against ethanol maceration (MCE). MCE yielded 17.10% crude extract, while CoS SCE at 35 MPa/60°C achieved 5.98%, but with higher enrichment of flavonoids (88 mg QE/g, 2.1-fold above MCE) and retention of lipophilic phytosterols and terpenoids. MCE remained superior in total phenolic and saponin extraction. The selected SCE extract demonstrated dose- and time-dependent cytotoxicity against HeLa cells (IC₅₀ = 158 µg/mL, 48 h), but limited selectivity over hTERT-HME1 cells (SI ≈ 1.2). These findings underscore CoS SCE as a greener, rapid method for selectively recovering moderately polar bioactives from <i>C. nutans</i>, warranting bio-guided fractionation to enhance therapeutic specificity.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"16 4","pages":"235-241"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12610283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512807","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":"Impact of Vitamin D status on age at menopause: A prospective cohort study.","authors":"Khalida Hassan Muho","doi":"10.4103/JAPTR.JAPTR_52_25","DOIUrl":"10.4103/JAPTR.JAPTR_52_25","url":null,"abstract":"<p><p>Calcium levels, closely tied to Vitamin D, significantly impact female health. However, the link between Vitamin D and menopause, its onset, and symptom severity remains unclear. This study aimed to examine the impact of Vitamin D supplementation on the age at menopause, menopausal symptoms, hormonal levels, and bone density in women. A 2-year prospective study of 100 menopausal women, grouped by Vitamin D levels (<20 ng/mL and >30 ng/mL), analyzed menopausal age, symptoms, hormone levels, and bone density. The results show that the women with vitamin D levels below 20 ng/mL had later menopause, more severe symptoms, lower estrogen, higher follicle-stimulating hormone, poorer bone density, and reduced quality of life than those with levels above 30 ng/mL, with all differences statistically significant (<i>P</i> < 0.05). Finally, I concluded that the vitamin D deficiency in menopausal women is linked to delayed menopause, severe symptoms, and poor hormonal and bone health. Adequate levels may support better menopausal health.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"16 4","pages":"190-194"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12610294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512852","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":"Investigation of antioxidant, anti collagenase, anti-elastase, and anti-hyaluronidase activities of <i>Solanum trilobatum</i> L. for pharmaceutical development.","authors":"Chanai Noysang, Monsicha Khuanekkaphan, Teerarat Pummarin, Wiphupat Buranasukhon, Em-On Chaiprateep","doi":"10.4103/JAPTR.JAPTR_148_25","DOIUrl":"10.4103/JAPTR.JAPTR_148_25","url":null,"abstract":"<p><p>The health and beauty sectors are significant drivers for the continuous growth of related product markets. <i>Solanum trilobatum</i> L. (<i>S. trilobatum</i>), locally known as Ma Waeng Krue, is a popular medicinal plant utilized in primary health care in Thailand. Renowned for their remarkable antimicrobial, antioxidant, antibacterial, and antifungal characteristics, the leaves and fruits of this plant yield abundant quantities of saponins, anthraquinones, terpenoids, and tannins. This study investigated the antioxidant activity, total phenolic content (TPC), and inhibitory effects of unripe and ripe <i>S. trilobatum</i> fruit extracts against collagenase, elastase, and hyaluronidase, specifically methanol and ethyl acetate extracts. The ethyl acetate extracts from unripe fruits contained the highest TPC and showed the greatest antioxidant activity as demonstrated by the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and ferric reducing antioxidant power methods. In contrast, methanol extracts from ripe fruits had the highest yield and demonstrated the greatest antioxidant activity according to the 2,2-diphenyl-1-picrylhydrazyl assay. Notably, methanol extracts from unripe fruits exhibited the most potent inhibition of collagenase, elastase, and hyaluronidase compared with ethyl acetate extracts.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"16 4","pages":"201-206"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12610293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512761","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":"Formulation of triphala-based products: Focus on gallic acid content and health benefits.","authors":"Em-On Chaiprateep, Chanai Noysang, Punyanut Amorndoljai, Khemjira Jarmkom, Monsicha Khuanekkaphan","doi":"10.4103/JAPTR.JAPTR_118_25","DOIUrl":"10.4103/JAPTR.JAPTR_118_25","url":null,"abstract":"<p><p>Triphala, a traditional Ayurvedic formulation comprising <i>Terminalia chebula</i>, <i>Terminalia bellirica</i>, and <i>Phyllanthus emblica</i>, is renowned for its rich phytochemical composition and numerous health benefits. This study developed and evaluated three triphala-based functional food products - beverages, gummies, and tablets - by measuring gallic acid content, nutritional composition, and microbiological safety. High-performance liquid chromatography analysis showed gallic acid levels of 5.35 ± 0.14 mg per 200 mL in beverages, 248 ± 4.38 mg per 25 g in gummies, and 783 ± 2.69 mg per 12 g in tablets. Each product complied with microbial safety standards and was fortified with essential nutrients, confirming its suitability as a safe and functional food. These formulations advance plant-based functional foods, promoting health and disease prevention.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"16 4","pages":"213-218"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12610291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512824","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":"Network pharmacology and molecular docking investigation of <i>Curcuma xanthorrhiza</i> Roxb. rhizome with the mechanisms underlying as the potential drug of eczema treatment.","authors":"Yusuf Alif Pratama, Honey Dzikri Marhaeny, Sulistyanengci Winarto, Igansius Agyo Palmado, Muhammad Hermawan Widyananda, Mahardian Rahmadi, Muhammad Taher, Ahmed Abdallah Hasan, Burkhard Kleuser, Junaidi Khotib","doi":"10.4103/JAPTR.JAPTR_117_25","DOIUrl":"10.4103/JAPTR.JAPTR_117_25","url":null,"abstract":"<p><p>A chronic inflammatory dermatosis, eczema, affects more than 12% of the pediatric population and 7.2% of adults. Clinically, it presents with erythematous, scaly, and intensely pruritic lesions. Severe forms of the disease frequently exhibit poor responsiveness to treatments aimed at a single inflammatory pathway. <i>Curcuma xanthorrhiza</i> Roxb. rhizomes possess antioxidant, anti-inflammatory, and anti-allergic activities through a multi-target mechanism. This study aimed to evaluate the secondary metabolites of <i>C. xanthorrhiza</i> Roxb. rhizomes that can be developed into eczema drugs using virtual screening <i>in silico.</i> Secondary metabolite compounds from <i>C. xanthorrhiza</i> rhizomes were evaluated for their drug-likeness properties Subsequently, the similarity of their physicochemical properties was assessed using the principal component analysis. A target search of drug candidates was performed using the Swiss Target Prediction and Gene Expression Omnibus (GEO) Omnibus. Docking was performed using Molegro by comparing the rerank scores of the drug candidates with those of the original ligands. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction was performed using the pkCSM. Carbonic anhydrase II, epidermal growth factor receptor, and the mammalian target of rapamycin came as the protein target for eczema disease. For the docking result, demethoxycurcumin (C00037023), 1,5-dihydroxy-1,7-bis (4-hydroxy-3-methoxyphenyl)-4,6-heptadien-3-one (C00055412), 1,7-bis (4-hydroxy-3-methoxyphenyl)-3,5-heptanediol (C00055175), and 3'-demethoxycyclocurcumin (C00054761) had both better rerank score than the native ligand and good ADMET profiles. Four compounds derived from <i>C. xanthorrhiza</i> Roxb. rhizomes can be developed as an eczema potential treatment.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"16 4","pages":"219-225"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12610289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512847","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":"Differences in microhardness and tensile strength of stainless steel temporary anchorage devices after exposure to fluoride, povidone-iodine, and chitosan solution.","authors":"Devina Elita, Haru Setyo Anggani, Nada Ismah","doi":"10.4103/JAPTR.JAPTR_131_25","DOIUrl":"10.4103/JAPTR.JAPTR_131_25","url":null,"abstract":"<p><p>Temporary anchorage devices (TADs) are widely utilized as supplementary anchorage in orthodontic treatment, offering several advantages alongside certain limitations. One such limitation is the potential for mechanical failure, which may occur due to a reduction in corrosion resistance. Recent studies have reported changes in the mechanical properties of TADs - notably decreased corrosion resistance - following exposure to mouthwash during orthodontic treatment. The objective of this study is the evaluation of corrosion resistance of stainless steel (SS) TADs by assessing changes in microhardness and tensile strength following <i>in vitro</i> exposure to mouthwashes. A total of 28 TADs were categorized into four distinct groups differentiated by the type of mouthwash utilized: Fluoride, povidone-iodine, chitosan, or distilled water (control group). Each TAD was placed in a centrifuge tube and immersed in the respective solution for 90 days. Changes in the mechanical aspects of the SS TADs were evaluated through the assessments of microhardness using the Vickers method and tensile strength using a tensile test. The highest microhardness value was observed in the chitosan group (435 VHN), followed by the fluoride group (429.71 VHN), the povidone-iodine group (429.29 VHN), and the distilled water group (420 VHN). Similarly, the highest tensile strength was recorded in the chitosan group (70.20 megapascal [MPa]), followed by the fluoride group (68.87 MPa), the povidone-iodine group (67.19 MPa), and the distilled water group (48.59 MPa). SS TADs exhibited superior mechanical properties after immersion in a chitosan solution, indicating their potential protective effect against corrosion-related degradation.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"16 4","pages":"207-212"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12610288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512890","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":"The efficacy of herbal medicine in the management of oral stomatitis in head and neck cancer patients undergoing radiotherapy: A systematic review.","authors":"Sry Suryani Widjaja, Imam Bagus Sumantri, Rusdiana Rusdiana, Tengku Helvi Mardani, Vito Filbert Jaylie, Lowilius Wiyono","doi":"10.4103/JAPTR.JAPTR_59_25","DOIUrl":"10.4103/JAPTR.JAPTR_59_25","url":null,"abstract":"<p><p>Radiotherapy for head-and-neck cancer (HNC) frequently causes oral mucositis, a painful and debilitating condition often leading to treatment interruption, poor quality of life, and increased healthcare costs. Various herbal medicines such as <i>Glycyrrhiza glabra</i> (<i>Yashtimadhu)</i>, <i>Plantago major L.</i> syrup, green tea mouthwash, and <i>Hangeshashinto</i> have been proposed for studies to explore the possibility of alleviating radiation-induced oral mucositis, with promising results serving as alternatives to conventional medication. This review assesses the effectiveness of Herbal preparations such as <i>G. glabra</i> (<i>Yashtimadhu</i>), <i>P. major L</i>., and traditional Chinese formulations like <i>Chining decoction</i> and <i>Hangeshashinto</i> which have shown promise in both preclinical and clinical studies in reducing the risk and impact of oral mucositis under radiation therapy. The results showed a wide variation in the efficacy of herbal treatments. Herbal medicine offers a promising adjunctive approach in the management of oral mucositis resulting from radiation therapy for HNC. Of all of these, <i>Yashtimadhu</i>, <i>P. major</i>, and <i>Hangeshashinto</i> were identified to demonstrate potential with statistically significant efficacy in reducing mucositis severity.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"16 4","pages":"171-176"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12610285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512936","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":"Bacterial and antibiotic susceptibility test patterns and quality of life of diabetic foot ulcer patients.","authors":"Rika Yulia, Heryanti Pusparisa, Farid Al Hasan, Fauna Herawati","doi":"10.4103/JAPTR.JAPTR_277_24","DOIUrl":"10.4103/JAPTR.JAPTR_277_24","url":null,"abstract":"<p><p>Antibiotic resistance is a growing concern in the treatment of diabetic foot ulcers. To address this, this study analyzed antibiotic usage patterns, microbial profiles, antimicrobial susceptibility, and patient quality of life (QoL). This was a descriptive observational study. This study collected data prospectively at Bojonegoro Regional Hospital between October 2022 and January 2023. Of the 66 patients, all of them exhibited bacterial growth. Microbial sensitivity profiles were categorized as gram-positive in 21 patients (32%), gram-negative in 38 patients (58%), gram-positive - gram-positive in 1 patient (2%), gram-negative - gram-negative in 2 patients (3%), and gram-positive - gram-negative in 4 patients (5%). The use of antibiotics is sensitive to gram-positive drugs, such as: cefepime, ceftriaxone, imipenem, and meropenem. Levofloxacin and imipenem both work 100% in gram-negative bacteria. Antibiotic usage overall is 159.05 DDD/100 patient days. Of the 11 highest domains, 33 patients (50.0%) have a good QoL, while 19 patients (28.8%) have poor QoL. A comprehensive approach is necessary for the effective management of diabetic foot wound infections, and family support is essential for the improved patient's QoL.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"16 4","pages":"195-200"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12610286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512874","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":"Antidiabetic potential of <i>Sapindus trifoliatus</i> fruit ethanolic extract: Gas chromatography-mass spectrometry profiling, molecular docking, and <i>in vitro/in vivo</i> evaluation.","authors":"Sarita Rawat, Prashant Kumar Dhakad, Ritu Gilhotra, Kavita Goyal, A Rekha, Mohit Rana, Rakhi Mishra, Lakshmi Thangavelu, Gaurav Gupta","doi":"10.4103/JAPTR.JAPTR_116_25","DOIUrl":"10.4103/JAPTR.JAPTR_116_25","url":null,"abstract":"<p><p>Diabetes mellitus causes vascular, renal, and ocular complications. In this study, we evaluated an ethanolic extract of <i>Sapindus trifoliatus</i> fruit using gas chromatography-mass spectrometry (GC-MS) profiling, molecular docking, and <i>in vitro</i> and <i>in vivo</i> assays. GC-MS analysis revealed key bioactive phytochemicals, and docking analysis demonstrated strong AKR1C3 binding. Acute toxicity testing confirmed safety at doses up to 5000 mg/kg. In alloxan-induced diabetic mice, extract treatment dose dependently lowered fasting blood glucose and HbA1c levels, restored pancreatic, hepatic, and cardiac histology, and mitigated ocular, renal, and cardiac damage. In <i>in vitro</i>, the extract inhibited α-amylase and α-glucosidase, supporting its antihyperglycemic activity. Compared to previous studies, <i>S. trifoliatus</i> extract showed enhanced efficacy, likely due to its antioxidant and anti-inflammatory properties, underscoring its potential as a plant-based antidiabetic therapy.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"16 4","pages":"226-234"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12610284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512949","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, toxicity, and cytotoxicity activities from dichloromethane root extract and fraction of <i>Rhizophora stylosa</i> Griff.","authors":"Nurdin Saidi, Binawati Ginting, Mustanir Yahya, Murniana Murniana, Agnia Purnama, Cantika Dwi Riski","doi":"10.4103/JAPTR.JAPTR_89_25","DOIUrl":"10.4103/JAPTR.JAPTR_89_25","url":null,"abstract":"<p><p><i>Rhizophora stylosa</i> Griff. roots contain bioactive metabolites and therapeutic potential. This study measured the antioxidants, toxicity and cytotoxicity from its dichloromethane extract and four derived fractions (RSD 1-4). The extracts showed strong antioxidant activity (IC₅₀ = 7.50 ppm) and toxicity (LC₅₀ = 31.92 ppm). Evaluation of each fraction showed that RSD 2 had the highest activity for antioxidant bioactivity with IC₅₀ of 45.40 ppm and toxicity with LC₅₀ value of 332.48 ppm. Cytotoxicity against MCF-7 cells showed that RSD 3 had the stronger effect, followed by RSD 2 with IC₅₀ values of 225.50 ppm and 155.90 ppm, respectively. Statistical analysis confirmed that differences in antioxidant and toxicity activities among extract and fractions were significant (<i>P</i> < 0.05), whereas cytotoxic activity differences were not statistically significant. Gas chromatography-mass spectrometry analysis of RSD 2 identified stigmasta-3,5-diene, α-amyrin, and lupeol as major components and potentially responsible for the bioactivities. In summary, dichloromethane root extract of <i>R. stylosa</i> Griff. may serve as phytomedicines for breast cancer.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":"16 4","pages":"177-182"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12610292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512902","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}