Mahdi Abdoli Shadbad, Roghaiyeh Derogar, Ali Akbar Shekarchi, Farideh Akbari, Mehri Jafari Shobeiri
{"title":"Mature cystic ovarian teratoma with squamous cell carcinoma transformation: a case report and literature review.","authors":"Mahdi Abdoli Shadbad, Roghaiyeh Derogar, Ali Akbar Shekarchi, Farideh Akbari, Mehri Jafari Shobeiri","doi":"10.1515/hmbci-2023-0001","DOIUrl":"10.1515/hmbci-2023-0001","url":null,"abstract":"<p><strong>Objectives: </strong>Cancerous transformation in mature cystic ovarian teratoma is rare. Herein, we reported a case of squamous cell carcinoma transformation in mature cystic ovarian teratoma and performed an in-depth literature review to highlight the risk factors, prognosis, and suggested treatment for these patients.</p><p><strong>Case presentation: </strong>We report a 66-years old postmenopausal woman diagnosed with a 120×90 (mm) mass at the left adnexa compatible with mature cystic ovarian teratoma. Following resection, the histopathological investigations showed malignant transformation in her mature cystic ovarian teratoma, and the immunohistochemistry for cytokeratin (CK) 5/6 and tumor protein 63 (P63) indicated squamous cell carcinoma transformation. She has been observed for her stage IA tumor and has been cancer-free for 6 months.</p><p><strong>Conclusions: </strong>Although malignant transformation in mature cystic ovarian teratoma is rare, it should be suspected if certain risk factors, e.g., elderly and high tumor size, exist. Stage IA patients' prognosis is favorable, and chemotherapy is not recommended.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":" ","pages":"35-39"},"PeriodicalIF":1.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570273","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":"Biological activities of African medicinal plants in the treatment of erectile dysfunction: a mechanistic perspective.","authors":"Olorunfemi Oyewole Babalola, Opeyemi Iwaloye, Paul Olamide Ottu, Precious Olayinka Aturamu, Femi Olawale","doi":"10.1515/hmbci-2022-0090","DOIUrl":"10.1515/hmbci-2022-0090","url":null,"abstract":"<p><p>The global incidence of erectile dysfunction is increasingly becoming a significant health concern, as its frequency demonstrates a consistent upward trajectory each year. In recent years, FDA-approved drugs like sildenafil among others has been approved to treat this disorder however the drug is not without its own side effects. In a bid to develop alternative therapeutic option, scientists have now turned to traditional medicine in search of a treatment regimen. Africa is blessed with numerous medicinal plants used in the treatment and management of several diseases including erectile dysfunction. Due to limited access to modern medicine and high-quality medical facilities, a significant number of individuals in Africa continue to depend on traditional medicine as a means of addressing critical health issues. Perhaps one of the grossly explored medicinal properties of plants in Africa is for erectile function. Through years of extensive research in medicinal plants, several plants indigenous to Africa have been identified to show profound ability to mitigate erectile dysfunction. While previous reports have indeed corroborated the ability of this plant to abate erectile dysfunction, there is still a dearth of information regarding the mechanistic aspect of these plants. Hence, the current review aims to provide a comprehensive mechanistic perspective to the major African medicinal plant which have been reported to be effective in the treatment of erectile dysfunction.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":" ","pages":"357-370"},"PeriodicalIF":1.0,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466604","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":"Effects of pioglitazone and linagliptin on glycemic control, lipid profile and hs-CRP in metformin-treated patients with type 2 diabetes: a comparative study.","authors":"Batool Zamani, Seyyed Mashaalah Tabatabizadeh, Hamidreza Gilasi, Shadi Yazdani","doi":"10.1515/hmbci-2022-0070","DOIUrl":"10.1515/hmbci-2022-0070","url":null,"abstract":"<p><strong>Objectives: </strong>The purpose of this study was to compare the effects of pioglitazone and linagliptin on glycemic control, lipid profile and high-sensitivity C-reactive protein (hs-CRP) parameters in patients with type 2 diabetes treated with metformin.</p><p><strong>Methods: </strong>The present randomized clinical trial was conducted on 60 patients with type 2 diabetes treated with metformin in the age range of 30-60 years. The participants with informed consent were randomly assigned to receive pioglitazone or linagliptin. The first intervention group (n=30) received 30 mg of pioglitazone daily and the second intervention group (n=30) received 5 mg of linagliptin daily for 12 weeks. Fasting blood samples were taken from patients at the baseline and after 12 weeks to measure related variables. The current study was approved in Kashan University of Medical Sciences (with the code of ethics of IR.KAUMS.MEDNT.REC.1398.016), and the Iranian Registry of Clinical Trials (with the registration number of IRCT20170513033941N66).</p><p><strong>Results: </strong>The linagliptin administration significantly reduced serum levels of fasting blood sugar (p=0.03), blood sugar 2 h after a meal (p=0.02), glycosylated hemoglobin (p=0.02) and hs-CRP (p=0.005) after 12 weeks compared with pioglitazone. In contrast, the pioglitazone administration significantly decreased triglyceride levels (p=0.01) and increased HDL-cholesterol (p=0.002) compared to linagliptin. In addition, the administration of both linagliptin and pioglitazone drugs had no significant effect on LDL-cholesterol, total cholesterol, systolic and diastolic blood pressure, creatinine and blood urea.</p><p><strong>Conclusions: </strong>The present study demonstrated the superiority of linagliptin over pioglitazone for glycemic control, although pioglitazone compared to linagliptin showed greater efficacy in reducing triglycerides and raising HDL-cholesterol.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":" ","pages":"385-391"},"PeriodicalIF":1.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032311","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}
Tomaz Jagric, Gaja Hladnik, Rok Kolaric, Marjeta Dugonik, Evgenija Homsak
{"title":"Does leptin cause proximal gastric cancer in the obese? The role of serum leptin in the etiology of proximal gastric cancer.","authors":"Tomaz Jagric, Gaja Hladnik, Rok Kolaric, Marjeta Dugonik, Evgenija Homsak","doi":"10.1515/hmbci-2022-0101","DOIUrl":"10.1515/hmbci-2022-0101","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of the present study was to determine the correlation between obesity, serum levels of leptin and proximal gastric cancer.</p><p><strong>Methods: </strong>Sixty-four gastric cancer patients operated on with curative intent were included in the study. We determined the correlation between the preoperative serum levels of leptin and the tumor's location.</p><p><strong>Results: </strong>Serum leptin levels were correlated significantly with the proximal third location (p=0.04), gastric outlet obstructing tumors (p<0.0001), CRP levels (p=0.03) and BMI (p<0.0001). Patients with high serum levels of leptin had significantly more intestinal types of gastric cancer (p=0.033) and better differentiation (p=0.009). The linear regression model determined the proximal tumor location (beta: 0.467; p=0.045), BMI (beta: 0.657; p=0.001), high preoperative serum albumin (beta: 0.563; p=0.016) and the presence of pyloric stenosis (beta: 0.525; p=0.006) as related significantly to serum leptin levels. The Cox proportional hazard model identified age (HR: 0.003; 95 % CI: 0-0.794; p=0.041), preoperative serum levels of leptin (HR: 0.125; 95 % CI: 0.018-0.887; p=0.037) and the number of extracted LNs (HR: 0.001; 95 % CI: 0-0.677; p=0.038) as independent prognostic factors.</p><p><strong>Conclusions: </strong>Serum levels of leptin were significantly elevated in patients with proximal gastric cancer, suggesting that the leptin's effect might be due to its systemic secretion. This might explain the higher incidence of proximal gastric cancer in obese patients. Elevated serum leptin levels were an independent prognostic factor.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":" ","pages":"393-400"},"PeriodicalIF":1.0,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138884885","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}
Jamal Amri, Mohammad Jamalian, Zahre Salami, Ahmad Akbari, Mona Alaee, Fatemeh Azizi Soleiman, Abbas Alimoradian
{"title":"Hydroalcoholic extract of <i>Scrophularia striata</i> has a significant therapeutic effect on thioacetamide-induced liver cirrhosis in rats.","authors":"Jamal Amri, Mohammad Jamalian, Zahre Salami, Ahmad Akbari, Mona Alaee, Fatemeh Azizi Soleiman, Abbas Alimoradian","doi":"10.1515/hmbci-2022-0106","DOIUrl":"10.1515/hmbci-2022-0106","url":null,"abstract":"<p><strong>Objectives: </strong>Liver cirrhosis is one of the most important causes of death from liver diseases. Nowadays, the use of herbal medicines has increased due to its availability, less side effects and cheapness for the treatment of liver diseases. The present study was conducted to examine therapeutic effects of hydroalcoholic extract of <i>Scrophularia striata</i> (<i>S. striata</i>) on thioacetamide-induced liver cirrhosis in rats through evaluate its effects on oxidative stress markers and the expression of metalloproteinase 1 (TIMP 1), toll-like receptor-4 (TLR-4), and Mitofusin (MFN2) genes.</p><p><strong>Methods: </strong>24 male rats were selected by simple random sampling. Rats were randomly assigned to four groups: group I: healthy rats, group II: thioacetamide (TAA) injected rats, group III: TAA injected rats+100 mg/kg bw of <i>S. striata</i> and group IV: TAA injected rats+200 mg/kg bw of <i>S. striata</i>. Liver cirrhosis was induced in rats by a 300 mg/kg bw TAA administration twice with an interval of 24 h. After 8 weeks of treatment by <i>S. striata</i> at doses of 100 and 200 mg/kg bw, biochemical factors and oxidative stress markers (SOD, TAC, GPX, CAT and MDA) were measured using spectrophotometric methods. Also, gene expression of TIMP 1, TLR-4, and MFN2 were analyzed using real-time PCR. ANOVA and Bonferroni post hoc test analysis were applied to evaluate the data.</p><p><strong>Results: </strong>The results showed the <i>S. striata</i> extract significantly improve the serum ALT, AST and ALP levels, TIMP 1, TLR-4, and MFN2 genes and oxidative stress markers (SOD, TAC, GPX, CAT and MDA) in the liver tissues when compared to control group (p<0.05). Also, it was found that the beneficial effects of the <i>S. striata</i> were dose-dependent.</p><p><strong>Conclusions: </strong>Based on the results obtained <i>S. striata</i> by reducing the expression of TIMP 1, TLR-4, and MFN2 genes and improving oxidative stress might be used as adjuvant treatment for liver cirrhosis.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":" ","pages":"371-377"},"PeriodicalIF":1.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138829494","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}
Siti Maisarah Ahmad, Norazilah Mat Jin, Mohd Faizal Ahmad, Abdul Kadir Abdul Karim, Muhammad Azrai Abu
{"title":"Unexplained subfertility: active or conservative management?","authors":"Siti Maisarah Ahmad, Norazilah Mat Jin, Mohd Faizal Ahmad, Abdul Kadir Abdul Karim, Muhammad Azrai Abu","doi":"10.1515/hmbci-2022-0087","DOIUrl":"10.1515/hmbci-2022-0087","url":null,"abstract":"<p><strong>Objectives: </strong>Unexplained subfertility (UEI) describes a couple whose standard subfertility workout consider acceptable but unable to conceived.</p><p><strong>Methods: </strong>This retrospective study was conducted in the Advanced Reproductive Centre, UKM Hospital, Kuala Lumpur, from January 2016 to December 2019. The data of 268 UEI couples were obtained from the clinical database. Women aged 21-45 years old was included and further divided into four groups according to the female partner's age and subfertility duration: group A (age <35 years and subfertility <2 years), group B (age <35 years and subfertility >2 years), group C (age >35 years and subfertility <2 years), and group D (age >35 years and subfertility <2 years). All statistical analyses were performed using SPSS 22.0 for Windows.</p><p><strong>Results: </strong>A total of 255 cases were included in this study. The mean age of the women was 32.9 ± 4.04 years, and the mean subfertility duration was 5.04 ± 2.9 years. A total of 51 (20 %) cases underwent timed sexual intercourse, 147 (57.6 %) cases had intrauterine insemination (IUI), whereas 57 (22.4 %) cases opted for <i>in vitro</i> fertilization (IVF). A total of 204 cases underwent active management (IUI/IVF), which showed a significant difference (p<0.05). Out of eight clinical pregnancies, half of them were from group B.</p><p><strong>Conclusions: </strong>Active management in younger women with a shorter subfertility duration revealed a better pregnancy outcome. Otherwise, individualized treatment should be considered in selecting a suitable treatment plan.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":" ","pages":"379-384"},"PeriodicalIF":1.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138829495","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":"Intermittent vs. continuous swimming training on adipokines and pro-inflammatory cytokines in metabolic syndrome experimental model.","authors":"Shila Nayebifar, Hossein Nakhaei, Zohreh Borhani Kakhki, Elham Ghasemi","doi":"10.1515/hmbci-2022-0004","DOIUrl":"10.1515/hmbci-2022-0004","url":null,"abstract":"<p><strong>Objectives: </strong>In this study, metabolic syndrome-affected rats were studied to examine how intermittent and continuous swimming training influenced adipokines and pro-inflammatory cytokines.</p><p><strong>Methods: </strong>Forty-eight male Wistar rats were randomized in this experimental study into four groups (n=8), including normal control (NC), metabolic syndrome (MS), continuous swimming training with metabolic syndrome (CT-MS: load 0-3% body mass, 5 d/wk, for 8 weeks), and intermittent swimming training with metabolic syndrome (IT-MS: load 5-16% body mass, 5 d/wk, for 8 weeks). The serum levels of metrnl, adipolin, irisin, leptin, TNF-α, and IL-6 were measured using the ELISA test.</p><p><strong>Results: </strong>The IT-MS and NC groups exhibited significantly lower leptin concentrations than the CT-MS group (p=0.001). The irisin, meteorin, and adipolin serum levels increased significantly in CT-MS and IT relative to the NC and CT-MS groups (p=0.001), with the changes being more pronounced in the IT group (p=0.05). TNF-α and IL-6 were inclined in the CT-MS group compared with the other three groups (p=0.001), while IL-6 was increased in the IT group (p=0.024).</p><p><strong>Conclusions: </strong>Intermittent swimming is more effective than continuous swimming training in improving adipokines in rats with metabolic syndrome.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":" ","pages":"321-328"},"PeriodicalIF":1.0,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10004986","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":"Increased expression of androgen receptor and PSA genes in LNCaP (prostate cancer) cell line due to high concentrations of EGCG, an active ingredient in green tea.","authors":"Nadereh Bakhshandeh, Maryam Mohammadi, Parisa Mohammadi, Elahe Nazari, Mehdi Damchi, Sajad Khodabandelu, Hossein Mokhtari","doi":"10.1515/hmbci-2022-0054","DOIUrl":"https://doi.org/10.1515/hmbci-2022-0054","url":null,"abstract":"<p><strong>Objectives: </strong>Androgen receptor (AR) play a key role in the onset and progression of prostate cancer. Epigallocatechin-3-gallate (EGCG) is a polyphenolic compound and the active ingredient in green tea, which is involved in modulating gene expression through epigenetic alterations. Previous studies have shown that EGCG at low concentrations reduces the expression of AR and prostate-specific antigen (PSA) in the LNCaP cell line of prostate cancer. In this study, the effect of higher EGCG concentrations on AR and PSA expression in LNCaP prostate cancer cell line was investigated.</p><p><strong>Methods: </strong>In this study, LNCaP prostate cancer cell line was used and after MTT test, concentrations of 40, 60 and 80 μg/mL EGCG were used for treatment. Then, the expression of AR and PSA genes was evaluated by RT-PCR. AR protein expression was also assessed by Western blotting.</p><p><strong>Results: </strong>The present study showed that treatment of LNCaPs cells by EGCG reduces cell proliferation. The IC50 value was 42.7 μg/mL under experimental conditions. It was also observed that EGCG at concentrations of 40 and 80 μg/mL increased the expression of AR and PSA (p<0.05).</p><p><strong>Conclusions: </strong>The present study showed that the effect of EGCG on AR expression was different at different concentrations, so that unlike previous studies, higher concentrations of EGCG (80 and 40 μg/mL) increased AR and PSA expression. It seems that due to the toxic effects of EGCG in high concentrations on cancer cells and the possibility of its effect on normal cells, more caution should be exercised in its use.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":"44 2","pages":"181-186"},"PeriodicalIF":1.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9729734","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}
Mahsa Mashayekhi, Milad Asadi, Shahriar Hashemzadeh, Amir Vahedi, Dariush Shanehbandi, Ahmad Faris Al-Omar, Morteza Akbari, Mortaza Raeisi
{"title":"Promoter methylation levels of <i>RASSF1</i> and <i>ATIC</i> genes are associated with lung cancer in Iranian patients.","authors":"Mahsa Mashayekhi, Milad Asadi, Shahriar Hashemzadeh, Amir Vahedi, Dariush Shanehbandi, Ahmad Faris Al-Omar, Morteza Akbari, Mortaza Raeisi","doi":"10.1515/hmbci-2022-0007","DOIUrl":"https://doi.org/10.1515/hmbci-2022-0007","url":null,"abstract":"<p><strong>Objectives: </strong>Epigenetic alterations like methylation of tumor suppressor genes or oncogenes, in respiratory epithelium have been associated with lung cancer. Hypermethylation of genes promoter is an epigenetic event, and is responsible to tumor suppressor genes inactivation as well as oncogenes activation. This study aimed to assess the role of methylation status in promoter of <i>RASSF1</i> and <i>ATIC</i> genes their potential implication in the pathogenesis of lung tumor in Iranian patients.</p><p><strong>Methods: </strong>In this study, we collected 100 tissue samples (50 lung cancer tissues and 50 adjacent non-cancerous lung tissues) from Iranian lung cancer patients. The genomic DNA was extracted, and methylation status of both <i>RASSF1</i> and <i>ATIC</i> genes was investigated by methylation-sensitive high-resolution melting (MS-HRM) assay technique and Real-Time PCR. Cancer Genome Atlas (TCGA) dataset was also analyzed for further validation of the gene's methylation.</p><p><strong>Results: </strong>Methylation of <i>RASSF1</i> gene promoter was significantly higher in lung tumor tissues. However, promoter methylation levels of <i>ATIC</i> gene was significantly lower in lung tumor tissues. These results were additionally confirmed by TCGA analysis. Promoter methylation of both <i>RASSF1</i> and <i>ATIC</i> genes was significantly associated with lymph node metastasis, and clinical stage of lung cancer. The receiver operating characteristic (ROC) curve analysis indicated a high accuracy of promoter methylation in these genes as a diagnostic biomarker for lung cancer.</p><p><strong>Conclusions: </strong>Methylation levels of both <i>RASSF1</i> and <i>ATIC</i> genes promoters were associated with lung cancer pathogenesis in Iranian population, and may be a suitable biomarker for diagnosis and prognosis of lung cancer in early stage of tumorigenesis.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":"44 2","pages":"145-152"},"PeriodicalIF":1.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9731643","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}