Biomedical research and clinical reviews最新文献

{"title":"The Missing Link in the Human Thermoregulation Systems","authors":"A. Ibraimov, S. Akhunbaev, O. Uzakov","doi":"10.31579/2692-9406/105","DOIUrl":"https://doi.org/10.31579/2692-9406/105","url":null,"abstract":"The study of human thermoregulation is one of the most developed areas of modern physiology and medicine. This is due to the important role of temperature in normal and pathological conditions. Directly or indirectly almost all systems and organs are involved in maintaining of relatively constant temperature in the body, since their normal functioning is closely related to the temperature of the internal environment (temperature homeostasis). Currently, the existence of two systems of thermoregulation is recognized: a physiological organ-based system with a center in the hypothalamus and a molecular system, which manifests itself in the form of the production of proteins (heat shock- and cold shock proteins) and by activation of RNA thermometers in response to heat or cold shock. Based on studies of the variability of chromosomal heterochromatin regions in the genome of human populations permanently living in various climatic and geographical conditions of Eurasia and Africa, as well as individuals well adapted to the extreme conditions of the high altitudes of the Pamirs and Tien-Shan (mountaineers) and the Far North (oil drillers of the Yamal Peninsula, Eastern Siberia), we came to the conclusion that, apparently, there is a third system of thermoregulation at the cellular level (cell thermoregulation). By cell thermoregulation, we mean the removal of excess heat from the nucleus of an interphase cell in order to avoid the harmful effects of high temperature on the complex molecular processes occurring in the nucleoplasm. We believe that some intracellular formations (a dense layer of condensed chromatin around the nucleus, nucleoli, chromocenters and other membraneless bodies) serve as a structural basis for the removal of heat from the cell nucleus, because the material basis of all these temporary structures in the interphase nucleus is the chromosomal heterochromatin regions. In this review, we discuss a set of data, which indicate that cell thermoregulation, may be a missing link between organism and molecular level in maintaining temperature homeostasis in the human body.","PeriodicalId":72392,"journal":{"name":"Biomedical research and clinical reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48429259","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":"Ayurvedic Formulations for the Treatment of Covid -19","authors":"Jangampally Vedhashree, R. Kirthi, A. Krishna sailaja, M. Suma kanth, Mallepally Deepa Reddy, M. Kumar","doi":"10.31579/2692-9406/108","DOIUrl":"https://doi.org/10.31579/2692-9406/108","url":null,"abstract":"Background and objective: To recognize natural phytochemicals from medicinal plants, in order to reutilize them against COVID-19 by the virtue of molecular dynamics (MD) simulation study and molecular docking study COVID-19 is a transmissible disease that is initiated and propagated through a new virus strain SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2). Since 31st December 2019 in Wuhan city of China and the infection has outspread globally infecting many countries. Methods: Molecular dynamics MD simulation interaction analysis, Salt bridge analysis, Flexibility analysis, Ace-2- rbd complex electrostatic component of binding energy calculation method. Results: Molecular docking studies has shown to be having two inhibitors against SARS-CoV-2 Mpro (Main protease), from Withania somnifera (Ashwagandha) (Withanoside V [10.32 kcal/mol] and Somniferine [9.62 kcal/mol]). Inconsolably, SARS-CoV-2 infection in patients with pre-existing disease conditions (e.g., hypertension and diabetes) can cause severe complications and, as a result, mortality. Conclusion: Hence from the present study it could be suggested that, the active phytochemicals from medicinal plants could potentially inhibit Mpro of SARS-CoV-2 and further equip the management strategy against COVID-19-a global contagion. Active phytoconstituents of Ayurvedic medicinal plants Withania somnifera (Ashwagandha) predicted to significantly hinder main protease (Mpro or 3Clpro) of SARS-CoV-2.Through molecular docking and molecular dynamic simulation study, Withanoside V, Somniferine were observed to impede the activity of SARS-CoV-2 Mpro.","PeriodicalId":72392,"journal":{"name":"Biomedical research and clinical reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45613907","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":"Human Chromosomal Q-heterochromatin Regions as a System","authors":"A. Ibraimov, S. Akhunbayev, O. Uzakov","doi":"10.31579/2692-9406/106","DOIUrl":"https://doi.org/10.31579/2692-9406/106","url":null,"abstract":"The eukaryotic genome consists of the two forms of chromatin: euchromatin and heterochromatin. The DNA of euchromatin contains the gene portion of the genome, while heterochromatin is represented predominantly from non-coding repetitive nucleotide sequences that do not encode proteins or enzymes. In higher eukaryotes, some part of the non-coding, highly repetitive nucleotide sequences were transformed into complex forms of DNA organization as chromosomal constitutive heterochromatin regions. There are two types of constitutive heterochromatin: C- and Q-heterochromatin. C-heterochromatin is found in the chromosomes of all eukaryotic cells, while Q-heterochromatin is found in the karyotype of only three higher primates (Homo sapiens, Gorilla gorilla and Pan troglodytes). Since the discovery of the position effect variegation phenomenon C-heterochromatin has been attributed to gene silencing effects. Dosage compensation of genes is another epigenetic gene silencing mechanism that makes it possible to equalize the level of expression of sex-linked genes in males and females. In mammals, this is done by inactivating one X chromosome in the cells of females using facultative heterochromatin, which is a heterochromatinized euchromatin. However, no epigenetic gene silencing was found in chromosomal Q-heterochromatin regions (Q-HRs). The question is discussed why human chromosomal Q-HRs does not exhibit gene silencing or other epigenetic effects and what their biological role might be.","PeriodicalId":72392,"journal":{"name":"Biomedical research and clinical reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45977727","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":"Efficacy and Safety of Tocilizumab in Severe Covid-19 Infection in Second and Third Wave of Epidemics in Myanmar: Multicenter Randomized Controlled Trial","authors":"K. Pyar, A. Kyaw, N. L. Maung, Z. Aung, Thida Tun, A. Thu, Zin Thu Aung, M. Shan, Y. Aung, K. Z. Lin, Si Phyo Thu, T. Kyaw, S. A. Hla, K. S. Win","doi":"10.31579/2692-9406/100","DOIUrl":"https://doi.org/10.31579/2692-9406/100","url":null,"abstract":"Background: Coronavirus disease 2019 (COVID-19), emerged in China at the end of 2019, became a major threat to health around the world as it caused significant morbidity and mortality. SARS-CoV-2 infection induces a cytokine storm due to dose-dependent production of IL-6 from bronchial epithelial cells; therefore, Tocilizumab, a monoclonal antibody against the interleukin-6 receptor, is one of the recommended drugs for treatment of COVID-19 infection. It may result in better outcomes in patients with severe Covid-19 infection. The efficacy and timing of Tocilizumab therapy in severe COVID-19 infection in Myanmar was not known clearly. Methods: A hospital based interventional study design (Randomized controlled trial) was conducted in COVID-19 treatment centers in Myanmar -Yangon and Nay Pyi Taw, from February 2020 to August 2021. Supervised treatment was done; and, both clinical and laboratory data were collected by using standardized forms and analysis was done. We conducted a double-blind, randomized, placebo-controlled trial of intravenous Tocilizumab in adults who were hospitalized with severe COVID-19 infection. Patients were randomly assigned to receive either Tocilizumab or placebo for within 5 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. Results: A total of 105 patients (55 in Tocilizumab group and 50 in Standard treatment group) with severe COVID-19 infection were included. Baseline characteristics in Tocilizumab group and Standard treatment group were as follows: (1) mean age 64.4 ± 11.9 years and 59.9 ± 15.8 years; (2) BMI 24.3 ± 3.0 and 23.9 ± 5.0; (3) mean duration of symptom onset to hospital admission was 9.5 ± 4.4 days and 6.5 ± 3.8; (4) mean duration of symptom onset to treatment was 12.8 ± 3.8 days and 7.1 ± 3.8 days; (6) mean duration of hospital stay was 20.1 ± 16.5 days and 11.4 ± 4.8 days; (7) associated co-morbidities was 88% and 70%; and, (8) mean CXR severity score by Braxia was 12.0 ± 2.0 and 9.6 ± 3.4 respectively. The survival rate in early treatment receiving group was 80% in Tocilizumab group and 65.5% in Standard treatment group; that of median treatment receiving group was 40% and 62.5% respectively. The survival rate in late treatment receiving group reduced to 36% in Tocilizumab group; however, no one survived in Standard treatment group. Inflammatory markers (Ferritin, LDH, D dimer and CRP) dropped significantly at 24 hours and 72 hours after Tocilizumab treatment; the difference was noticeable between survivors and non-survivors. Absolute lymphocyte count, liver enzymes (AST and ALT) and procalcitonin levels became normal by 2 weeks. No significant changes were seen in serum creatinine and blood urea level. Both clinical observation and questioning on experienced side effects from patients on recovery revealed that Tocilizumab therapy was tolerable and safe. Conclusions: Tocilizumab treatment was associa","PeriodicalId":72392,"journal":{"name":"Biomedical research and clinical reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42877831","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":"Quantum-Information Processes in Awareness Management","authors":"A. Adamski, Julia Adamska","doi":"10.31579/2692-9406/104","DOIUrl":"https://doi.org/10.31579/2692-9406/104","url":null,"abstract":"Human mental life is a form of existence of information not only electromagnetic, but also acoustic, spin, soliton and bioplasm. That is, the layout the biological human in addition to the biochemical way uses the message of information using energy and information converters in living cells. The human biological system creates the pictorial structure of the world not only through sensory perception, but also on the basis of soliton, spin and bioplasm waves. The action of solitons in the biological system of man gives the basis for seeing the psychobiological structures of man in a different light, as presented in biology, medicine and psychology. The science to date recognizes only the action of an electromagnetic wave on the sense of sight. It can be concluded that we are dealing with a second center that creates the structure of the world image and is responsible for health and the development of diseases in humans. According to the authors, consciousness cooperates with the cosmos and is guided by the laws of quantum mechanics. Under its law, there is room for artificial consciousness. In their deliberations, the authors will understand that it is a dynamic structure of quantum-cybernetic-information team processes taking place in the bioplasm of the brain, which is in synergistic interaction with biocomputer simulation, guided by the emission of coherent light, modulated by a soliton wave.","PeriodicalId":72392,"journal":{"name":"Biomedical research and clinical reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45299822","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":"Attitudes and Behaviors of Healthcare Professionals toward HIV Positive Patients in a Tertiary Hospital","authors":"E. Jacob, Osime E. O, Fasakin Kolawole, Oyedele Titilayo E","doi":"10.31579/2692-9406/094","DOIUrl":"https://doi.org/10.31579/2692-9406/094","url":null,"abstract":"Background: In reality, fear of being infected at work has led to stigmatization and discriminatory treatment of HIV/AIDS patients. The consequence of such negative attitude is poor management of people with HIV/AIDS who need most care, treatment, and support. Aim: To evaluate attitudes and behaviors of healthcare professionals toward HIV/AIDS patients in a tertiary hospital in Nigeria Methodology: This was a cross-sectional study conducted in Federal Teaching Hospital, Ido-Ekiti, Nigeria. 250 healthcare professionals were selected randomly, Participants completed a well-structured, self-administered questionnaire delivered to them at their workplace. Data obtained from the questionnaire was analyzed using SPSS software version 9. Results: A total of 250 healthcare professionals participated in the study, 148(59.2%) were males and 102 (40.8%) were females. 153(61.2%) of them had been working between 0- 10 years with prevalence age group 30-40 years. Majority of Healthcare professionals (HCPs) in this study demonstrated positive attitude and behaviour toward HIV/AIDS patients. However, minority of HCPs had negative attitudes toward HIV/AIDS patients by agreed to the statements that HCPs should not share office with HIV patients, beds of HIV patients should be marked and HCPs should allow relation to marry HIV patients. Conclusion: Healthcare professionals should have access to up-to-date information on all aspects of HIV/AIDS through effective training on the modes of HIV transmission, prevention, counselling, guidelines for safe practice and the rights of PLWHIV, this would reduce discriminatory attitudes towards PLWHIV and also improve patients' care and access to quality healthcare services.","PeriodicalId":72392,"journal":{"name":"Biomedical research and clinical reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42449840","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":"Physico-Chemical Properties of Indigofera Zollingeriana Seed Oil","authors":"A. J.O, Adedeji .M.O, H. Z., N. Glória, Dabara Comfort Wyedia","doi":"10.31579/2692-9406/099","DOIUrl":"https://doi.org/10.31579/2692-9406/099","url":null,"abstract":"The objective of the present study is to examine the physico-chemical properties of Indigofera zollingeriana seed oil. Physico-chemical parameters of oils are important in the determination of edibility and other industrial applications. All the laboratory analysis were carried out using standard procedures according to AOAC (2000). The acid value, peroxide value, iodine value, saponfication value, refractive index and free fatty acids of cold pressed Indigofera zollingeriana seed oil was found to be 17.11 mg NaOH/g, 23.04 meq/kg, 180.4 gI2/100g, 118.7 mg/KOH/g and 14.10 %. The refractive index (20oC) and specific gravity (25oC) was 2.01 and 1.02 respectively. The extracted oil was Indigo in colour at liquid state. It was concluded the oil has a high acid value, peroxide value and free fatty acid which favours the use of the oil for industrial use such as soap production and cosmetics.","PeriodicalId":72392,"journal":{"name":"Biomedical research and clinical reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42343631","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":"Classification of Absolute Cd4+ T Lymphocytes Count in Immunological, Virological and Erythropoietic Growth Factor among HIV Infected Patients","authors":"E. Jacob, Osime E. O, Ogunbusuyi Bolu Esther, Oyegue Kelvin, Oyedele Titilayo E","doi":"10.31579/2692-9406/095","DOIUrl":"https://doi.org/10.31579/2692-9406/095","url":null,"abstract":"Background: HIV-infection resulted in CD4+ T-cell depletion which is accompanied by an increase in CD8+ T-cells resulting in an inverted CD4/CD8 ratio. Low CD4/CD8 ratio has been identified as a hallmark of inmmunosenescence and a surrogate of mortality in HIV infected patients especially in ART-naïve patients Aim: Classification of absolute CD4+ T-lymphocytes count in immunological, virological and erythropoietic growth factor among HIV infected patients Methodology: One hundred samples each was collected from HIV positive subjects on ART and HIV positive subjects ART naïve. Six milliliters of whole blood was collected from each consented subject, 3ml was dispensed into 5ml K2EDTA bottle for immediate analysis of absolute CD4 count, CD8 count, total white cell count and HIV screening. The remaining 3ml of blood was dispensed into plain bottle; serum was extracted for the analysis of erythropoietin and viral load Results: Mean values of CD8, CD4/CD8, EPO and TWBC in CD4 <200 were significantly (p<0.05) lower compared to CD4 >500 and CD4 200-499. Mean values of VL in CD4 <200 were significantly (p<0.05) higher compared to CD4 >500 and CD4 200-499 among HIV subjects on ART and ART-naïve Conclusion: Immunological and erythropoetic growth factor assessed in this study were decline while viral load was increasing as HIV infection progresses with depletion in absolute CD4 count, this study shows the efficacy of ART on the treated subjects. However, based on this study, absolute CD8 T cells count, CD4/CD8 ratio and erythropoietin can be used as surrogate makers to ascertain pathogenesis in HIV-infected subjects.","PeriodicalId":72392,"journal":{"name":"Biomedical research and clinical reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48074434","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":"Intractable/ Persistent Hiccups Due to Acute Subdural Haemorrhage as a Result of Prolonged Inr in a 55 Year Old Man with Rheumatic Mitral Valvular Heart Disease and Atrial Fibrillation: A Case Report","authors":"K. Pyar, S. A. Hla, W. Myint, Win Kyaw Shwe, S. Hlaing, Zaw Min Tun, Han Lin Aung, Phyo Htet Oo, Kyaw Zayar Lin, Moe Tun Zaw, Kyaw Zay Ya, Myo Thant Kyaw, Nay Myo Aung, Than Naing Lin, Soe Moe Htun, Zay Phyo Aung","doi":"10.31579/2692-9406/089","DOIUrl":"https://doi.org/10.31579/2692-9406/089","url":null,"abstract":"A 58 year old man was brought to hospital in state of deep coma following severe headache for one day. His GCS was 3/15 and had flaccid all 4 limbs with equivocal planter response on both sides on arrival. NECT head showed acute subdural haemorrhage with surrounding cerebral oedema, mid-line shift and corning of brain stem. After giving mannitol and dexamethasone, four hours later, he became fully conscious and orientated; his motor power returned to normal. He was on warfarin 3mg daily for rheumatic mitral valvular heart disease with atrial fibrillation and his INR on arrival was 3.5. He had intractable hiccups once he regained consciousness. Both pharmacological and non-pharmacological measures were tried for distressing hiccups; there was no therapeutic success. His hiccups disappeared completely only after removing the haematoma by burr hole surgery.","PeriodicalId":72392,"journal":{"name":"Biomedical research and clinical reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45401964","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":"Changes in the Serum Levels of Estradiol and Changes in Expression of Estrogen Receptor Alpha in the Bone Tissue of Ovariectomized Wistar Rats","authors":"Armine V. Grigoryan, Alexander B. Blazhev, Tatyana M. Betova, Aneliya A. Dimitrova","doi":"10.31579/2692-9406/091","DOIUrl":"https://doi.org/10.31579/2692-9406/091","url":null,"abstract":"Estradiol is an estrogen steroid hormone and is produced basically within the follicles of the ovaries. The decrease in serum estrogens concentration at menopause disrupts the metabolic balance, changes the lipid profile leading to visceral obesity, which caused an increase in serum estradiol levels, through aromatase activity. Estrogen deficiency also is a reason for the development of osteoporosis.We investigated the serum estradiol levels and changes in bone alpha estrogen receptor expression in ovariectomized rats. For this purpose, we used 20 female Wistar rats at reproductive age - 2 months divided into 2 groups: group 1 (G1)-10 animals were ovariectomized and group 2 (G2)-10 of which were sham-operated. All animals of G1 showed weight gain compared to group G2. The results showed that the values of serum 17β-estradiol in rats of G1 statistically increased compared to G2 (p <0.05). Immunohistochemical analysis revealed no difference in estrogen receptor expression between the both groups. Histomorphological analysis of femur from G1 showed the presence of pronounced osteoporosis. Ovariectomy led to the development of obesity, which caused an increase in serum estradiol levels, through aromatase activity, but this process did not prevent bone tissue from developing osteoporosis.","PeriodicalId":72392,"journal":{"name":"Biomedical research and clinical reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49026187","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}