bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Mesenchymal Stem Cells Promote Ischemic Repairment and Angiogenesis of Diabetic Foot Through Exosome miRNA-21-5p
Authors: Huang Chen , Luo Wenfeng , Wang Qian , Ye Yufeng , Fan Jinghui , Lin Li , Shi Congying , Wei Wei , Chen Hanwei , Wu Yangzhe , Tang Yukuan 
Published: July 2020

Abstract
Background: Diabetic foot is caused by ischemic disease of lower extremities of diabetic patients, and the effective therapy is very limited. Mesenchymal stem cells (MSCs) based cell therapy had been developed into a new treatment strategy for diabetic foot clinically. However, the underlying molecular mechanism remains to be fully addressed. Exosomes secreted by MSCs may play crucial role in the processes of MSCs mediated inhibition of inflammatory microenvironment as well as pro-angiogenesis of ischemic tissue of diabetic foot. Methods: Exosomes were isolated from MSCs using ultra-high centrifugation, and further characterized by the nanoparticle tracking analyzer and flow cytometry. Moreover, RNA sequencing, Western Blot, in vitro cell proliferation, in vivo pro-angiogenesis, as well as ischemic repairment of diabetic foot through rat model were performed to evaluate exosome physiological functions. Results: We found that different inflammatory cytokines (tumor necrosis factor a, vascular cell adhesion molecule-1 and interleukin-6) induced MSCs to secrete exosomes heterogeneously, including exosome size and quantity. Through RNA sequencing, we defined a new proangiogenic miRNA, miRNA-21-5p. Further knockdown and overexpression of miRNA-21-5p by manipulating MSCs validated the biological activity of exosome miRNA-21-5p, including in vitro cell proliferation, in vivo pro-angiogenesis in Chick Chorioallantoic Membrane (CAM) assay, and in vivo pro-angiogenesis experiments (tissue injury and repair) in diabetic rat models. Furthermore, we discovered that exosomemiRNA-21-5p promoted angiogenesis through upregulations of vascular endothelial growth factor receptor (VEGFR) as well as activations of serine/threonine kinase (AKT) and mitogen-activated protein kinase (MAPK). Together, our work suggested miRNA-21-5p could be a novel mechanism by which exosomes promote ischemic tissue repairing and angiogenesis. Meanwhile, miRNA-21-5p could be potentially developed into a new biomarker for exosomes of MSCs to treat diabetic foot. Conclusions: miRNA-21-5p is a new biomarker and a novel mechanism by which exosomes promote ischemic tissue repairing and angiogenesis of diabetic foot. Our work could not only provide new scientific evidences for revealing pro-angiogenesis mechanism of MSCs, but also eventually benefit MSCs-based clinical therapy for diabetic foot of diabetes patients.
Subcutaneous injection of interferon-α2b for COVID-19: an observational study
Authors: Wang Bo , Li Diandian , Liu Tao , Wang Haohua , Luo Fengming , Liu Yanbin 
Published: July 2020

Abstract
Background
The global pandemic of coronavirus disease 2019 (COVID-19) infection is ongoing and associated with high mortality.
Objective
The aim of this study was to investigate the efficacy and safety of subcutaneous injection of interferon-α2b (IFN-α2b) combined with lopinavir/ritonavir (LPV/r) in the treatment of COVID-19 infection, compared with that of using LPV/r alone.
Methods
Patients diagnosed with laboratory-confirmed COVID-19 infection in Wuhan Red Cross hospital during the period from January 23, 2020 to March 19, 2020 were included. The length of stay, the time to viral clearance and adverse reactions during hospitalization were compared between patients using oral LPV/r and combined therapy of LPV/r and subcutaneous injection of IFN-α2b.
Results
A total of 22 patients were treated with LPV/r alone and 19 with combined therapy with subcutaneous injection of IFN-α2b. The average length of hospitalization in the combination group (16 ± 9.7 days) was shorter than that of LPV/r group (23±10.5 days). Moreover, the days of hospitalization in early intervention group decreased from 25 ± 8.5 days to 10 ± 2.9 days compared with delayed intervention group. Combined therapy with IFN-α2b also significantly reduced the duration of detectable virus in the upper respiratory tract. No patient in each group was transferred to intensive care unit (ICU) or died during the treatment. There was no significant difference in the adverse effect composition between two groups.
Conclusion
Subcutaneous injection of IFN-α2b combined with LPV/r might shorten the length of hospitalization and accelerate viral clearance in COVID-19 patients, which deserves further investigation in clinical practice.
Effects of Chromosomal Abnormalities on Assisted Reproductive Technology: A Retrospective Cohort Study
Authors: Cui Ling , Lin Yonghong , Wang Fang , Yu Xinting , Teng Wending , Xian Hong , LI Min 
Published: July 2020

Abstract
Background: To ascertain whether couples with chromosomal abnormalities have a difference in cumulative clinical pregnancy rate and cumulative live birth rate among assisted reproductive technology population. Methods: Design: A retrospective cohort study. Setting: Department of reproduction and infertility in Chengdu Women's and Children's Central Hospital.Patients: A total of 112 couples were in exposed group with chromosomal abnormalities and 226 couples without chromosomal abnormalities in control group included in the study, totaling 338 cases. From 1st Jan 2017 to 31st Dec 2019. Control group (infertility couples without chromosomal abnormalities) was 1:2 matched by female age, type of infertility (primary, secondary), type of assisted reproductive technology (IVF, ICSI or IUI). Results: Primary outcomes: cumulative clinical pregnancy rate and cumulative live birth rate. The results indicated that chromosomes abnormalities had no statistical difference in primary outcomes. Further analysis revealed exposed group (couples with chromosomal abnormalities) had less 2 pronuclear stage count. The times of embryo transfer by ICSI was less than IVF in exposed group. We found out only female age had an effect on the primary results and the threshold was 33.5years old.Conclusions: There were no significant differences in cumulative clinical pregnancy rate and cumulative live birth rate between two groups. But 2 pronuclear stage count, and the times of embryo transfer were affected by chromosomal abnormalities. It may be better to choose ICSI and PGT in this population.
Regional differences between superficial and deep lumbar multifidus in patients with chronic lumbar spine pathology
Authors: Padwal Jennifer , Berry David B , Hubbard James C. , Zlomislic Vinko , Allen R. Todd , Garfin Steven R. , Ward Samuel R. , Shahidi Bahar 
Published: July 2020

Abstract
Background: Due to its unique arrangement, the deep and superficial fibers of the multifidus may have differential roles for maintaining spine stabilization and lumbar posture; the superficial multifidus is responsible for lumbar extension and the deep multifidus for intersegmental stability. In patients with chronic lumbar spine pathology, muscle activation patterns have been shown to be attenuated or delayed in the deep, but not superficial, multifidus. This has been interpreted as pain differentially influencing the deep region. However, it is unclear if degenerative changes affecting the composition and function of the multifidus differs between the superficial and deep regions, an alternative explanation for these electrophysiological changes. Therefore, the goal of this study was to investigate macrostructural and microstructural differences between the superficial and deep regions of the multifidus muscle in patients with lumbar spine pathology.Methods: In 16 patients undergoing lumbar spinal surgery for degenerative conditions, multifidus biopsies were acquired at two distinct locations: 1) the most superficial portion of muscle adjacent to the spinous process and 2) approximately 1 cm lateral to the spinous process and deeper at the spinolaminar border of the affected vertebral level. Structural features related to muscle function were histologically compared between these superficial and deep regions, including tissue composition, fat fraction, fiber cross sectional area, fiber type, regeneration, degeneration, vascularity and inflammation. Results: No significant differences in fat signal fraction, muscle area, fiber cross sectional area, muscle regeneration, muscle degeneration, or vascularization were found between the superficial and deep regions of the multifidus. Total collagen content between the two regions was the same. However, the superficial region of the multifidus was found to have less loose and more dense collagen than the deep region. Conclusions: The results of our study did not support that the deep region of the multifidus is more degenerated in patients with lumbar spine pathology, as gross degenerative changes in muscle microstructure and macrostructure were the same in the superficial and deep regions of the multifidus. In these patients, the multifidus is not protected in order to maintain mobility and structural stability of the spine.
Chemical composition and pharmacological mechanism of Ephedra-Glycyrrhiza drug pair against coronavirus disease 2019 (COVID-19)
Authors: Qiu Qin , Li Mingyue , Lin Haowen , Cao Shilin , Wang Qu , Li Xiaoling , Chen Zishi , Jiang Wenhao , Huang Yuge , Luo Hui , luo lianxiang 
Published: July 2020

Abstract
Background: Coronavirus disease 2019 (COVID-19) is currently spreading all over the world, and the prospect of a very rapid increase in COVID-19 cases prompted us to seek effective antiviral therapeutics, from the identification of possible drugs to their potential mechanisms. Purpose: The aim of this study was to explore the efficacy of the Ephedra-Glycyrrhiza (EG) drug pair on coronavirus disease 2019 (COVID-19) by network pharmacology and molecular docking. Methods: The main active compounds, target information, meridians and properties of EG were obtained through the TCMSP and ETCM databases. The targeted information of COVID-19 was acquired from the GeneCards database. EG drug pair applied diseases were analysed by DAVID and the drug-bank database, and visualized by Rstudio and Cytoscape 3.7.2. Then, we carried out targeted intersection of the EG drug pair and COVID-19 to map the compound-target-disease interactions and visualize them with Cytoscape 3.7.2 and Venny 2.1. In addition, the enrichment analysis of the GO and KEGG pathways were visualized with Rstudio and PathVisio software through the DAVID database. Finally, we carried out the molecular docking of the EG active compounds with M hydrolase (Mpro), spike protein (S protein) and angiotensin-converting enzyme 2 (ACE2), and the binding modes between GE and the protein were verified via molecular dynamics (MD) simulation. Results: We identified 112 active EG compounds by network pharmacological analysis. Drug pair enrichment analysis demonstrated that these compounds may participate in the cAMP, PI3K-Akt, JAK-STAT and chemokine signalling pathways, which had a high correlation with respiratory system, nervous system, blood circulation system and digestive system related diseases. Pathway analysis between EG and COVID-19 showed that the key targets were TNF, IL2, FOS, ALB and PTGS2. They may regulate the PI3K-Akt signalling pathway and natural killer cell-mediated cytotoxicity to play roles in immune regulation, organ protection, antiviral, immune regulation, and organ protection as well as having antiviral effects. Molecular docking results showed that the active EG compounds bind well to Mpro, S protein and ACE2. The binding modes between the active compounds of the EG and protein were verified via MD simulation. Conclusion: The EG drug pair can treat COVID-19 through multiple targets and pathways, which can provide a theoretical basis for further study of the mechanism of action of the EG drug pair on COVID-19.
Exploration in the mechanism of fucosterol for the treatment of non-small cell lung cancer Based on network pharmacology and molecular docking
Authors: Li Xiaoling , Lin Baixin , Lin Zhiping , Wang Qu , Zheng Yushi , Cui Liao , Luo Hui , luo lianxiang 
Published: July 2020

Abstract
Background: It has been demonstrated that fucosterol induces a therapeutic effect on cancer. However, the molecular mechanisms underlying the effects of fucosterol in the treatment of non-small cell lung cancer are still unclear.Methods: In this study, pharmMapper and GeneCards databases were utilized to gather the prediction of fucosterol targets and NSCLC-related targets. The mechanisms of fucosterol against NSCLC were identified in DAVID6.8 by enrichment analysis of GO and KEGG, and protein-protein interaction data was obtained from Sting Database. Molecular docking was used to predict the docking of GRB2. Moreover, the relationship of GRB2 expression and immune infiltrates was analyzed by TIMER database.Results: The results suggest that fucosterol acts against by candidate targets, such as MAPK1, EGFR, GRB2, IGF2, MAPK8 and SRC, which regulate biological processes including negative regulation of apoptotic process, peptidyl-tyrosine phosphorylation, positive regulation of cell proliferation. The Raf / MEK / ERK signaling pathway initiated by GRB2 maybe the most significant pathway for fucosterol to treat NSCLC.Conclusions: These results show that GRB2 is the key target for fucosterol in the treatment of NSCLC, which laying a theoretical foundation for further research and providing scientific support for the development of new drugs.
Fluoroscopy-assisted percutaneous guide wire puncture for the treatment of intertrochanteric fractures with proximal femur nail anti-rotation
Authors: Xu Huazhong , Yuan Peng , Yang Yusheng , Shi Ke-qin 
Published: July 2020

Abstract
Background: Accurate percutaneous guide wire insertion for the treatment of intertrochanteric fractures with proximal femur nail anti-rotation(PFNA) can be a technical challenge. It is critical for the surgeon to place the implant accurately during the procedure; however, the muscles and soft tissues in the hip often make accurate guide wire insertion difficult, especially in overweight and obese patients.Purposes: The purpose of this study was to evaluate a series of patients who underwent percutaneous guide wire puncture and PFNA fixation to determine the influence of this technique on soft-tissue trauma and accuracy of guide wire placement.Methods: From June 2015 to June 2018,forty-five consecutive patients with a minimally displaced or displaced intertrochanteric fracture were treated with percutaneous guide wire puncture technique and PFNA fixation in two trauma centers. Six patients were lost to follow-up. The remaining thirty-nine patients were followed until union or a minimum of twelve months. There were thirty female and fifteen male patients with a mean age of 78.5 years old. Radiographs were used to evaluate the quality of fracture union. Intraoperative fluoroscopic views of the first puncture attempt were evaluated for the accuracy of percutaneous puncture technique.The number of puncture attempts used was recorded.Incision lengths of nail insertion were measured and recorded.Results: All fractures united. The length of the incisions ranged from 2.0 cm to 3.1 cm,with a mean of 2.5 cm.The angles between the guide wire and the axis of the proximal femur were within 3°in lateral fluoroscopic view,and ranged from 4°to 8°with a mean value of 6.3°in anteroposterior(AP) fluoroscopic views.The number of punctures in every patient were less than 2.Among forty-five patients, forty-three patients(95.6%) were punctured successfully with one pass. No complications were observed.Conclusions: Percutaneous guide wire puncture for the treatment of intertrochanteric fractures with PFNA fixation can lead to excellent outcomes, by virtue of accurate implant placement, less trauma,and fewer complications.Level of Evidence: Therapeutic level IV
Genomic Survey Sequencing, Development and Characterization of Single- and Multi-Locus Genomic SSR Markers of Elymus Sibiricus L.
Authors: Xiong Yi , Lei Xiong , Bai Shiqie , Xiong Yanli , Liu Wenhui , Wu Wendan , Yu Qingqing , Dong Zhixiao , Yang Jian , Ma Xiao 
Published: July 2020

Abstract
Background: Siberian wildrye (Elymus sibiricus L.) attracts considerable interest for grassland establishment and pasture recovery in the Qinghai-Tibet Plateau (QTP) due to its excellence in strong stress tolerance, high nutritional value and ease to cultivate. However, the lack of genomic information of E. sibiricus hampers its genetics study and breeding process.Results: In this study, we performed a genome survey and developed a set of SSR markers for E. sibiricus based on Next-generation sequencing (NGS). We generated 469.17 Gb clean sequence which is 58.64× of the 6.86 Gb estimated genome size. We assembled a draft genome of 4.34 Gb which has 73.23% repetitive elements, a heterozygosity ratio of 0.01% and GC content of 45.68%. Based on the gnomic sequences we identified 67,833 SSR loci and from which four hundred were randomly selected to develop markers. Finally, 30 markers exhibited polymorphism between accessions and ten were identified as single-locus SSR. These newly developed markers along with previously reported 30 ones were applied to analyze genetic polymorphism among 27 wild E. sibiricus accessions. We found that single-locus SSRs are superior to multi-loci SSRs in effectiveness.Conclusions: This study provided insights into further whole genome sequencing of E. sibiricus in strategy selection. The novel developed SSR markers will facilitate genetics study and breeding for Elymus species.
Screening of Non-catalytic Integrase Inhibitors for Anti-HIV Drug Development
Authors: Park Ki Hoon , Kim Minjee , Bae Seoung Eun , Lee Hee Jung , Kim Kyung-Chang , Choi Byeong Sun , Kim Young Bong 
Published: July 2020

Abstract
Background: Integrase (IN) is an essential protein for HIV replication that catalyzes insertion of the reverse-transcribed viral genome into the host chromosome during the early steps of viral infection. Highly active anti-retroviral therapy (HAART) is a HIV/AIDS treatment method that combines three or more antiviral drugs often formulated from compounds that inhibit the activities of viral reverse transcriptase and protease enzymes. Early IN inhibitors (INIs) mainly serve as integrase strand transfer inhibitors (INSTI) that disrupt strand transfer by binding the catalytic core domain (CCD) of IN. However, mutations of IN can confer resistance to INSTI. Therefore, non-catalytic integrase inhibitors (NCINI) have been developed as next-generation INIs. Methods: In this study, we evaluated and compared the activity of INSTI and NCINI according to the analysis method. Antiviral activity was compared using p24 ELISA with MT2 cell and TZM-bl luciferase system with TZM-bl cell. Each drug was serially diluted and treated to MT2 and TZM-b1 cells, infected with HIV-1 AD8 strain and incubated for 5 and 2 days, respectively. Additionally, to analyze properties of INSTI and NCINI, transfer inhibition assay and 3'-processing inhibition assay were performed. Results: During screening of INIs using the p24 ELISA and TZM-bl luciferase systems, we found an inconsistent result with INSTI and NCINI drugs. Following infection of MT2 and TZM-bl cells with T-tropic HIV-1 strain, both INSTI and NCINI treatments induced significant p24 reduction in MT2 cells. However, NCINI showed no antiviral activity in the TZM-bl luciferase system, indicating that this widely used and convenient antiretroviral assay is not suitable for screening of NCINI compounds that target the second round of HIV-1 replication. Conclusion: Accordingly, we recommend application of other assay procedures, such as p24 ELISA or reverse transcription activity, in lieu of the TZM-bl luciferase system for preliminary NCINI drug screening. Utilization of appropriate analytical methods based on underlying mechanisms is necessary for accurate assessment of drug efficacy.
Using mobile phone data for epidemiological simulations of lockdowns: government interventions, behavioral changes, and resulting changes of reinfections
Authors: Müller Sebastian A , Balmer Michael , Charlton Billy , Ewert Ricardo , Neumann Andreas , Rakow Christian , Schlenther Tilmann , Nagel Kai 
Published: July 2020

Abstract
Epidemiological simulations as a method are used to better understand and predict the spreading of infectious diseases, for example of COVID-19. This paper presents an approach that combines person-centric data-driven human mobility modelling with a mechanistic infection model and a person-centric disease progression model. Results show that in Berlin (Germany), behavioral changes of the population mostly happened before the government-initiated so-called contact ban came into effect. Also, the model is used to determine differentiated changes to the reinfection rate for different interventions such as reductions in activity participation, the wearing of masks, or contact tracing followed by quarantine-at-home. One important result is that successful contact tracing reduces the reinfection rate by about 30 to 40%, and that if contact tracing becomes overwhelmed then infection rates immediately jump up accordingly, making rather strong lockdown measures necessary to bring the reinfection rate back to below one.
Productivity Growth and Sectoral Interactions under Domar Aggregation: A Study for the Brazilian Economy from 2000 to 2014
Authors: Santini Theo , Araujo Ricardo 
Published: July 2020

Abstract
In this paper, we use the Domar aggregation approach to study the evolution of productivity growth in Brazil from 2000 to 2014, thus allowing us a disaggregated assessment of the issue. We found that the overall performance of the Brazilian economy can be explained not only by the poor performance of its sectors but also in terms of diminishing industrial density, with fewer backward and forward connections amongst industries in terms of chains of intermediate inputs. Besides, despite the relatively high density of the manufacturing sector, it performed a negative role concerning aggregate productivity growth both directly and indirectly. Directly insofar as that sector had negatives productivity growths during the period under consideration, and indirectly due to its high interconnection, which spread negative rather than positive productivity gains across the economy. Therefore, to improve the poor performance of the Brazilian economy, it is mandatory to restore the capability of the manufacturing sector of yielding and spreading productivity gains.