{"title":"Effect of <i>Asplenium nidus</i> ethanolic extract on nociception using a <i>Caenorhabditis elegans</i> model","authors":"Michael Roy Vencer Malaluan, Paul Mark B. Medina","doi":"10.4314/tjpr.v22i8.14","DOIUrl":"https://doi.org/10.4314/tjpr.v22i8.14","url":null,"abstract":"Purpose: To investigate the antinociceptive effect of Asplenium nidus ethanolic extract (ANEE) using a Caenorhabditis elegans model.Methods: Sublethality assay was performed on ANEE to determine the experimental concentrations to be used for the antinociceptive assays. Antinociceptive effect of ANEE in C. elegans was investigated using mechanosensation assays in four treatment timepoints within 72 hours. Antinociceptive index (AI) was calculated for the cells treated with ANEE cells as well as morphine, paracetamol and control (1% DMSO).Results: The mechanosensation assays revealed that ANEE (104, 103, 102 μg/mL) had a significantly higher antinociceptive index (AI) (p<0.05) compared to the vehicle control (1% DMSO). The antinociceptive effects of ANEE, 2.5 μM morphine, and 0.01% mg/mL paracetamol in C. elegans were not significantly different (p>0.05). This effect of ANEE continued after four treatments within a 72-hour period.Conclusion: The findings revealed that A. nidus ethanolic extract (ANEE) possesses antinociceptive effect which validates folkloric use of A. nidus and suggest a potential for chronic therapeutic use.","PeriodicalId":23347,"journal":{"name":"Tropical Journal of Pharmaceutical Research","volume":"44 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135485724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hong Chen, Huifang Xiong, Chunmei Chen, Liping Fan
{"title":"Effect of carboprost tromethamine and carbetocin on coagulation factors and prognosis in puerpera with postpartum hemorrhage due to uterine inertia","authors":"Hong Chen, Huifang Xiong, Chunmei Chen, Liping Fan","doi":"10.4314/tjpr.v22i8.17","DOIUrl":"https://doi.org/10.4314/tjpr.v22i8.17","url":null,"abstract":"Purpose: To determine the effect of carboprost tromethamine and carbetocin on coagulation factors and prognosis in puerpera with postpartum hemorrhage due to uterine inertia.Methods: A total of 80 high-risk pregnant women with postpartum hemorrhage due to uterine inertia admitted to Longyan First Hospital Affiliated of Fujian Medical University, Longyan, China from June 2021 to June 2022 were randomly divided into control group (oxytocin + carboprost tromethamine, n = 40) and study group (oxytocin + carboprost tromethamine + carbetocin, n = 40). Vaginal bleeding volume was recorded for both groups at delivery, and 2 and 24 h after delivery. Decrease in hemoglobin level 24 h after delivery, as well as levels of coagulation factors, and adverse drug reactions before and after treatment were assessed.Results: The third stage of labor, postpartum hemorrhage at 2 and 24 h, and decrease in hemoglobin 24 h after delivery in the study group were lower (p < 0.05). Compared with that before treatment, PLT and FIB levels also fell, while APTT and PT levels rose in both groups after treatment for 24 h (p < 0.05). Platelet count and fibrinogen levels in the study group were lower after treatment for 24 h, but APTT and PT levels were higher (p < 0.05). There was no statistically significant difference in the incidence of adverse drug reactions between both groups (15.00 vs 12.50 %; p > 0.05).Conclusion: Co-administration of carboprost tromethamine with carbetocin prevents high-risk postpartum hemorrhage in pregnant women due to uterine inertia. It also reduces the level of bleeding, and promotes recovery of coagulation function. However, further clinical trials on a larger scale are recommended prior to the application of this treatment strategy in clinical practice.","PeriodicalId":23347,"journal":{"name":"Tropical Journal of Pharmaceutical Research","volume":"12 9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135484831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wesam M Salama, Sabry A El-Naggar, Barakat M ALRashdi
{"title":"<i>In vivo</i> anti-tumor effect of Egyptian scorpion <i>Leiurus quinquestriatus</i> venom in Ehrlich ascites carcinomabearing mice","authors":"Wesam M Salama, Sabry A El-Naggar, Barakat M ALRashdi","doi":"10.4314/tjpr.v22i8.15","DOIUrl":"https://doi.org/10.4314/tjpr.v22i8.15","url":null,"abstract":"Purpose: To investigate the anti-tumor efficacy of scorpion Leiurus quinquestriatus venom (LQV) in Ehrlich ascites carcinoma (EAC) mouse model.Methods: Mice were divided into 4 groups (n = 8), with Group 1 as negative control. Groups 2 to 4 mice were inoculated with EAC cells (1 x 106/mouse) intraperitoneally (ip). Group 2 mice were untreated while groups 3 and 4 mice were injected with 2 mg/kg of cisplatin (Cis) and 0.025 mg/kg of LQV ip, respectively, for 7 days. Tumor profile, as well as hematological and biochemical analyses were carried out.Results: Tumor volume and tumor cell counts decreased significantly (p < 0.05) following LQV treatment. Also, LQV potentiated necrosis, apoptosis and arrested tumor cells in the G0 and S-phases. Furthermore, it upregulated apoptotic-related gene (Bax and caspase-3) expressions and down-regulated anti-apoptotic gene (bcl-2) expression in EAC cells (p < 0.05).Conclusion: LQV has potential anti-tumor activity against EAC cells in mouse models. Therefore, it should be further investigated in vivo as an anti-tumor agent.","PeriodicalId":23347,"journal":{"name":"Tropical Journal of Pharmaceutical Research","volume":"208 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135484651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sanggenon C inhibits proliferation of breast cancer cells and reduces HIF-1α/VEGF pathway activity under hypoxia conditions","authors":"Junyuan Qu, Jing Li, Yongqiang Ma, Zhihui Wang","doi":"10.4314/tjpr.v22i8.4","DOIUrl":"https://doi.org/10.4314/tjpr.v22i8.4","url":null,"abstract":"Purpose: To evaluate the function and mechanism of sanggenon C (SC) on breast cancer (BC) cells.Methods: The effect of SC on malignant processes of BC was studied through cell counting kit-8, colony formation, flow cytometry, Transwell, wound-healing and western blot experiments. Besides, the related mechanism of action was explored using western blot assay.Results: SC reduced the cell viability of MDA-MB-231 and MCF-7 cells with half-maximal concentration of (IC50) value of 17.09 and 17.32 μM, respectively. SC also decreased the area ratio of colonies in the plate, but increased the apoptosis and G0/G1 phase arrest in both cell lines. Furthermore, SC decreased the number of invasion cells, but elevated the relative wound width of both cells. Moreover, SC treatment neutralized the hypoxia-induced level of HIF-1α/VEGF signaling.Conclusion: SC suppresses proliferation, mobility and invasion, but induces apoptosis and G0/G1 phase arrest in BC cells, as well as deceased HIF-1α/VEGF pathway activity under hypoxia conditions. The findings of this study reveal that SC is a potential agent for BC management.","PeriodicalId":23347,"journal":{"name":"Tropical Journal of Pharmaceutical Research","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135485739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Embelin enhances the osteogenic potential of LPS-induced periodontal ligament stem cells by activating AMPK and SIRT1","authors":"Lijian Wang, Weidong Wu, Xiaoying Wei","doi":"10.4314/tjpr.v22i8.5","DOIUrl":"https://doi.org/10.4314/tjpr.v22i8.5","url":null,"abstract":"Purpose: To investigate the role of embelin in periodontal ligament stem cells (PDLSCs) in an in vitro model of periodontitis.Methods: Lipopolysaccharide (LPS)-stimulated PDLSCs was used to construct a periodontitis cell model. PDLSCs in the treatment group were pretreated with different concentrations of Embelin, and CCK-8 and TUNEL staining were used to analyze cell viability and apoptosis. Enzyme-linked immunosorbent assay (ELISA) kits were used to evaluate the levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, and MCP-1) while reactive oxygen species levels were assessed by 2',7'- dichlorodihydrofluorescein diacetate (DCFH-DA) staining. Subsequently, osteogenic marker, ALP activity and protein expression levels of Runx2, OCN and BMP-2 in PDLSCs were evaluated by western-blot assay; AMPK and SIRT1 levels were also determined using Western blot assay.Results: Embelin pretreatment inhibited PDLSCs apoptosis, inflammatory factors, and oxidative stress, but up-regulated ALP, Runx2, OCN, and BMP-2 levels (p < 0.05). In addition, AMPK phosphorylation and SIRT1 protein levels were regulated by embelin (p < 0.05).Conclusion: Embelin exerts anti-inflammatory, anti-oxidative and osteogenic differentiation effects in LPS-induced PDLSCs cells in vitro by activating AMPK/SIRT1 signaling. Therefore, the compound has potentials for use in the management of periodontitis.","PeriodicalId":23347,"journal":{"name":"Tropical Journal of Pharmaceutical Research","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135485141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Studies on <i>in vitro</i> binding of parecoxib to p38MAPK using spectroscopic methods","authors":"Xuejie Li, Kun Huang, Shan Zhong","doi":"10.4314/tjpr.v22i8.16","DOIUrl":"https://doi.org/10.4314/tjpr.v22i8.16","url":null,"abstract":"Purpose: To investigate the interaction between parecoxib and p38MAPK under simulated physiological conditions.Methods: The interaction between parecoxib and p38MAPK was studied under simulated physiological conditions using spectroscopy-based methods. The effect of parecoxib on the microenvironment and conformation of p38MAPK chromophore was studied by synchronous fluorescence spectroscopy, three-dimensional fluorescence, time-resolved fluorescence spectroscopy, circular dichroism spectroscopy, and ultraviolet-visible absorption spectroscopy.Results: Synchronous fluorescence spectroscopy showed that addition of parecoxib changed the structure of p38MAPK and destroyed the original stable structure. Three-dimensional fluorescence spectroscopy showed that the hydrophilicity of the microenvironment in which the fluorescent chromophore is located was enhanced, and the polarity increased such that the serum protein macromolecules tend to be unfolded, and the alpha-helix content reduced. Time-resolved fluorescence spectroscopy showed that the presence of parecoxib hardly affected the fluorescence quenching of p38MAPK, and the combination of parecoxib and p38MAPK forms a stable complex (static quenching). Circular dichroism spectroscopy revealed the combined parecoxib change, the secondary structure of p38MAPK and reduced the alpha-helix content. Ultraviolet-visible absorption spectroscopy revealed changes in the microenvironment of the three amino acid residues as well as the tertiary structure of the protein.Conclusion: The results shows that parecoxib has a significant effect on the structure of p38MAPK. In addition to explicitly inhibiting COX-2 and blocking arachidonic acid synthesis of prostaglandins, it inhibits the pathway involved in p38MAPK.","PeriodicalId":23347,"journal":{"name":"Tropical Journal of Pharmaceutical Research","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135484829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nicotinamide phosphoribosyltransferase inhibitor is a potential therapeutic target in LPS-induced human trophoblast cell injury","authors":"Zuoman Zhang, Lijun Tang, Meifang Huang, Guangliang Bi, Weimin Huang","doi":"10.4314/tjpr.v22i8.8","DOIUrl":"https://doi.org/10.4314/tjpr.v22i8.8","url":null,"abstract":"Purpose: To investigate the role of nicotinamide phosphoribosyltransferase (NAMPT) in lipopolysaccharide (LPS)-induced damage in trophoblastic HTR-8/SVneo cells (HTR8 cells), with the aim of ultimately providing new therapeutic targets of preeclampsia (PE).Methods: Trophoblastic HTR-8/SVneo was cultured and treated with LPS to mimic PE in vitro, while FK866, an antagonist of NAMPT, was used to establish an inflammatory model of HTR8 cells. Western blot, enzyme-linked immunosorbent assay (ELISA) and quantitative real-time-polymerase chain reaction (qRT-PCR) were used to evaluate inflammatory response in HTR8 cells, and cell counting kit-8 (CCK8) and oxidative stress kits were performed to quantify cell activity in HTR cells.Results: Compared with the control group, the administration of LPS significantly increased the expression levels of NAMPT in HTR8 cells. FK866 suppressed the expression levels of proinflammatory factors IL-1β, TNF-α and IL-6, and alleviated inflammation by inhibiting NAMPT-mediated NF-κB pathway. The antioxidant effect of FK866 was achieved via activation of antioxidant proteins,catalase (CAT) and glutathione (GSH).Conclusion: FK866 protects HTR8 cells from LPS-induced inflammation and oxidative stress through the inhibition of NAMPT-NF-κB signaling pathway. Thus, NAMPT is a potential therapeutic target for preeclampsia (PE).","PeriodicalId":23347,"journal":{"name":"Tropical Journal of Pharmaceutical Research","volume":"2013 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135485145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Litian Zhou, Jiajia Xu, Jian Hu, Jiao Lei, Pinglai Yang
{"title":"Effect of remifentanil co-administered with propofol on stress response and postoperative complications in patients with cerebral hemorrhage undergoing surgical anesthesia","authors":"Litian Zhou, Jiajia Xu, Jian Hu, Jiao Lei, Pinglai Yang","doi":"10.4314/tjpr.v22i8.27","DOIUrl":"https://doi.org/10.4314/tjpr.v22i8.27","url":null,"abstract":"Purpose: To determine the anesthetic effect and related indicators following concurrent administration of remifentanil and propofol in cerebral hemorrhage surgery patients.Methods: A total of 88 cerebral hemorrhage patients admitted in Lishui People’s District Hospital, Nanjing, China, from December 2019 to December 2020, were assigned to two groups, viz, control group which received fentanyl and propofol for anesthesia, while study group was administered remientanil combined with propofol for anesthesia There were 44 patients in each group. Hemodynamic index, brain injury marker index, stress response index, awakening condition, propofol dosage, anesthetic effect, and adverse reactions were assessed and recorded.Results: Heart rate (HR), diastolic blood pressure (DBP), and systolic blood pressure (SBP) at T2 and T3 of the two groups were less than those at T1. At T3, the study group’s HR, DBP, and SBP were substantially higher than those of control group (p < 0.05); At 12 and 24 h after operation, brain injury markers and stress response indices in study group were significantly lower compared to control group (p < 0.05), while in comparison to control group (79.55 %), the degree of anesthesia in the study group was higher (95.45 %; p < 0.05). The incidence of adverse reactions in the study group (15.91 %) was lower than in control group (43.18 %; p < 0.05).Conclusion: Remifentanil, when combined with propofol anesthesia, stabilizes hemodynamics, protects against brain injury, and reduces stress reactions in patients undergoing cerebral hemorrhage surgery. The combination is also highly effective and safe. However, validation of these findings in larger clinical trials is required.","PeriodicalId":23347,"journal":{"name":"Tropical Journal of Pharmaceutical Research","volume":"44 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135484644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficacy of the combination of valsartan and hydrochlorothiazide in the treatment of hypertensive heart disease","authors":"Xin Zhou, Yuefeng Chu","doi":"10.4314/tjpr.v22i8.28","DOIUrl":"https://doi.org/10.4314/tjpr.v22i8.28","url":null,"abstract":"Purpose: To investigate the effectiveness of the combination of valsartan and hydrochlorothiazide in managing hypertensive heart disease.Methods: From August 2020 to October 2022, the case data of 120 patients in Lu’an Hospital of Anhui Medical University, Lu’an, China were analyzed retrospectively. Based on the different treatment options, 54 patients with hypertensive heart disease who received valsartan alone (80 mg, once daily) for 3 months were placed in control group (CG), while 66 patients who received valsartan combined with Systolic blood pressure (SBP), therapeutic effect, diastolic blood pressure (DBP), and incidence of adverse effects were also recorded for CG and SG.Results: In the SG, there were significant reductions in SBP, DBP, LVMI and LVPWT compared to CG, while EF showed significant increase after treatment (p < 0.05). In both groups, SBP, DBP, LVMI and LVPWT decreased significantly after treatment compared to pre-treatment values, but EF however showed a significant increase (p < 0.05). In the SG, there was a significant increase (p < 0.05) in the total effective rate compared to CG and there was also a significant reduction (p < 0.05) in the total incidence of adverse effects compared to CG.Conclusion: Valsartan combined with hydrochlorothiazide is more effective in treating patients with hypertensive heart disease than valsartan monotherapy alone. However, the combination treatment should be subjected to further clinical trials prior to its introduction into clinical practice.","PeriodicalId":23347,"journal":{"name":"Tropical Journal of Pharmaceutical Research","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135484647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fan Yang, Juan Zhang, Biao Xian, Yanping Zhang, Liangxin Zhai, Tong Yan, Lunhua Chen
{"title":"Effect of trichostatin A on biological characteristics of side population cells of cervical cancer cell line (HeLa)","authors":"Fan Yang, Juan Zhang, Biao Xian, Yanping Zhang, Liangxin Zhai, Tong Yan, Lunhua Chen","doi":"10.4314/tjpr.v22i8.12","DOIUrl":"https://doi.org/10.4314/tjpr.v22i8.12","url":null,"abstract":"Purpose: To investigate the effect of trichostatin A (TSA) on biological characteristics of side population (SP) cells of cervical cancer cell line (HeLa)Methods: Side population (SP) and NSP cells were obtained from 6th generation of primary cervical cancer cells and cervical cancer cell line (HeLa). Cell surface markers (ATP-binding membrane transporter superfamily G member 2 (ABCG2), CD133, CD43, p63, Ki67, multidrug resistance (MDR) as well as cell cycle phase distribution and apoptosis, were determined. SP cells in HeLa were divided into 3 groups that received TSA at doses of 0.01, 0.05, and 0.2 μM. Untreated cells served as control. Cell growth inhibition rates of different dose groups were compared. SP cells in HeLa were divided into simple irradiation group and combined irradiation group TSA (10 % inhibition concentration (IC10) + irradiation, and values of SP cell survival fraction (SF) of the two groups under different irradiation conditions were compared.Results: The content of SP in HeLa cell line was significantly higher than in cervical cancer tissue (p > 0.05). There were no significant differences in expression levels of ABCG2, CD133, CD43, p63, Ki67, and MDR, as well as G0/G1, S, and G2/M phase distributions and apoptosis rate between HeLa cell line and cervical cancer tissue (p > 0.05). On the 3rd, 5th, and 7th day, SF value of SP cells was significantly higher in NSP cells (p > 0.05). With increasing concentration of TSA, SF value of NSP cells gradually decreased, while that of SP cells did not change significantly.Conclusion: Cervical cancer cell line (HeLa) contains SP cells which have biological characteristics of tumor stem cells. Moreover, TSA exerts good cytotoxicity and radio-sensitization effect on SP cells.","PeriodicalId":23347,"journal":{"name":"Tropical Journal of Pharmaceutical Research","volume":"57 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135484648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}