bluuebunny/crossref_metadata_2025 huggingface dataset:
Live Birth Rate and Neonatal Outcomes of Different Quantities and Qualities of Frozen Transferred Blastocyst in Patients Requiring Whole Embryo Freezing Stratified by Age
Authors: Chen Shiping , Du Hongzi , Liu Jianqiao , Liu Haiying , Li Lei , He Yuxia
Published: July 2020

Background: Multiple pregnancies are associated with significant complications and health risks for both the mothers and infants. Single blastocyst transfer (SBT) is a logical and effective measure to reduce the incidence of multiple pregnancy with assisted reproductive technology (ART). Whether it is suitable for everyone undergoing SBT was inconclusive, in view of the consideration of embryo quality and patients’ age.Objective: To explored live birth rate (LBR) and neonatal outcomes of different quantities and qualities of blastocysts in patients stratified by age, using a cutoff of 35 years, who required whole embryo freezing and underwent a subsequent frozen-thawed transfer (FET) cycle.Methods: A total of 3362 patients were divided into five groups: group A (n=1569) received a single good-quality blastocyst; group B (n=1113) received two good-quality blastocysts; group C (n=313) received one good- and one average-quality blastocyst; group D (n=222) received two average-quality blastocysts; and group E (n=145) received one average-quality blastocyst. Results: For patients have good-quality blastocysts, irrespective of age, the LBR of double blastocyst transfer (DBT) were about 50-65% and multiple pregnancy rate (MPR) were 40-60%, however, the LBR of single blastocyst transfer (SBT) were 40-55% and MPR were 3.5-6.3%. For patients who only had average-quality blastocysts, the MPR of double average-quality blastocysts transfer was as high as 30-50%. Moreover, about 70-90% of preterm births resulted from multiple pregnancies, and about 85-95% of low birth weight babies come from multiple pregnancies. The neonatal outcomes (gestational age, birth weight and birth height ) of SBT were significantly lower than those of DBT regardless of age, and this statistical difference disappeared if the patients were sub-grouped by singleton or twin. There is no significant difference in neonatal outcomes between single good-quality blastocyst and single average-quality blastocyst transfer. Conclusions: SBT is a preferable option for patients regardless of age when good-quality blastocysts are available. For patients who only had average-quality blastocysts, patients should be informed that DBT was associated with higher multiple pregnancy and adverse neonatal outcomes when compared with SBT regardless of age, suggesting that the practice of SBT is also feasible for these patients.
Effect of miR-181b on the biological characteristics and clinical drug resistance of small cell lung cancer by targeting gene ACE2
Authors: Liu Huining , Su Jianling , Han Shaohui , Yin Qifan , Wang Yuexin
Published: July 2020

Objective To clarify the effect of miR-181b on the biological function of SCLC, to detect and verify its downstream target gene ACE2, and to explore the effect of clinical resistance on SCLC in order to find new specific diagnostic markers and therapeutic targets.Methods 1. Collect blood samples from 30 SCLC patients and 30 normal persons in our department from 2017 to 2019 to detect the expression level of miR-181b; 2. Detect the expression level of miR-181b in SCLC cells by RT-PCR, and Screening of downstream target genes used by gene chip, verification with luciferase and Western Blot; 3. Collect the general data of 30 SCLC patients and 30 healthy people (control group)，the patients were diagnosed by pathology and undergoing EC protocol in the Department of Thoracic Surgery and Oncology of our hospital to detect the expression level of mir-181b in different periods; 4. In the SCLC cell line and the SCLC mouse model constructed, different concentrations of EC chemotherapy and ACEI drugs were administered to detect the sensitivity of drug resistance and non-drug resistance.Results 1. The expression level of miR-181b in SCLC patients was lower than normal people; 2. The expression level of miR-181b in SCLC cell lines was lower than normal cells; ACE2 was verified as a downstream target of miR-181b by gene chip screening; 3. miR-181b is low-expressed in SCLC patients, first-line chemotherapy can promote its recovery, but cannot repair to normal levels, and miR-181b has a certain effect on SCLC chemotherapy sensitivity; 4. miR-181b can enhance the drug sensitivity of SCLC drug-resistant cells, the application of ACEI should increase the risk of SCLC drug-resistant.Conclusion 1. miR-181b has a low expression level in SCLC, and it can directly target the gene ACE2 to affect the biological characteristics of SCLC; 2. miR-181b is lowly expressed in SCLC patients, and first-line chemotherapy can promote it recovery, but cannot repair to normal levels, and ACEI drugs can increase the risk of SCLC drug-resistant.
Signal Reconstruction with Semidefinite Relaxation Optimization in Uplink Massive MIMO Systems
Authors: Li Guo
Published: July 2020

In this paper, we consider a single group massive MIMO system, which consists of one receiver (base station) deployed with a large number of antennas and multiple users with each having single antenna. In the uplink transmissions from users to base station, we focus on an efficient signal reconstruction of all the users' transmitted symbols. We build a statistic decision matrix based on the received signals, whose eigenvectors and eigenvalues constitute the key components of our signal reconstruction algorithm. Then, an optimization problem is formulated and we convert this problem to two sub-problems: obtaining the optimal weights by solving Semidefinite Relaxation (SDR) optimization and obtaining the optimal rotation phases. Finally, an iterative algorithm framework is proposed for multi-user signal reconstruction. Numerical results are also carried out to verify the bit-error-ratio (BER) performance compared with the several coherent detection schemes and the noncoherent transmission schemes.
Value of endobronchial cryotherapy in the management of malignant endobronchial obstruction in patients with inoperable NSCLC: A prospective analysis of clinical and survival outcomes
Authors: Rashad Alaa , Badawy Mohamed Shahat , Ali Mohammed Mustafa , Mansour Haggagy , Bary Mohamed Abdel
Published: July 2020

Background: Malignant endobronchial obstruction (MEBO) is the most debilitating complication in non-small cell lung cancer (NSCLC). The therapeutic role of cryotherapy and its impact on survival has not been well addressed. This is to clarify whether the combination of endobronchial cryotherapy (EBCT) and chemoradiotherapy (CRT) improved the outcomes in inoperable NSCLC patients with symptomatic MEBO compared to that obtained by CRT alone.Methods: A prospective ranomized cohort study included 60 cases presented to Qena University Hospital, Egypt, between December 2016 and May 2019. Group A included 30 patients were managed with EBCT plus CRT. Group B included 30 patients were managed with CRT alone. The outcomes assessed were symptoms relief, respiratory function tests (RFT), performance status and survival outcomes at baseline and 4 weeks of follow-up.Results: Group A patients showed a highly significant improvement in symptoms, RFT, 6MWD test and arterial blood gases, compared to group B. The mean Karnofsky score increased from 57.33±5.67 % at baseline to 60.67±6.39 % post-EBCT (P=0.036); group A was significantly improved compared to group B (P=0.04). The Kaplan-Meier median survival for all patients was 9.7±0.4 months (95% CI= 8.86-10.54), and group A cases (10.77±0.44 months, 95% CI= 9.9 -11.6) was significantly longer than that of group B cases (8.6±0.68 months, 95% CI= 7.3-9.97; T-test = 2.631, P= 0.011). Conclusion: The use of EBCT with CRT for the management of MEBO in symptomatic patients with inoperable NSCLC is an efficient and safe procedure. EBCT improves the clinical outcomes, RFT, performance status and median survival.
Serum IGFBP-2 in Systemic Sclerosis as a Protective Factor of Lung Dysfunction
Authors: Guiot Julien , Njock Makon-Sébastien , André Béatrice , Gester Fanny , Henket Monique , Seny Dominique de , Moermans Catherine , Malaise Michel G. , Louis Renaud
Published: July 2020

Background Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapid evolving interstitial lung disease (SSc-ILD), driving its mortality. Specific biomarkers associated with the progression of this lung disease are highly needed. We aimed to identify specific biomarkers of SSc-ILD to predict the evolution of the disease.Methods We compared prospectively serum levels of several biomarkers associated with lung fibrosis in SSc patients (n = 102) compared to healthy subjects (HS) (n = 39). We also performed a longitudinal study in a subgroup of 28 patients analyzing biomarkers variations and pulmonary function tests over a period of 2 years. Furthermore, we performed in vitro analysis to study the impact of Insulin like Growth Factor Binding Protein (IGFBP)-2 on fibrotic activity of human lung fibroblasts.Results Serum levels of IGFBP-1, IGFBP-2, interleukin-8 and matrix metallopeptidase-9 were significantly increased in SSc patients compared to HS while IGF-1 and IGFBP-3 were reduced. The variation of IGFBP-2 between baseline and 2-year follow-up was positively correlated with pulmonary function (assessed by carbon monoxide transfer coefficient (KCO)) at 2-year follow-up (r = 0.6, p < 0.001). Receiver operating characteristic curve analysis enabled us to identify that baseline IGFBP-2 < 105 ng/ml was associated with a better outcome (low risk to display KCO < 70% predicted) at 2-year follow-up (area under the curve = 0.75 at 75% sensibility and 68% specificity, p < 0.05). In vitro functional study showed that IGFBP-2 significantly reduced fibroblast proliferation and pro-fibrotic activity.Conclusions We showed for the first time that serum levels of IGFBP-2 might predict the evolution of SSc-ILD. Baseline IGFBP-2 above 105 ng/ml might be a prognostic factor of alveolo-capillary dysfunction.
Research on Active Compounds of Huanglian Jiedu Decoction for the Treatment of Corona Virus Disease 2019 Based on Network Pharmacology and Molecular Docking
Authors: Liu Leping , Xu Xinyi , Cao Xueshuai , Long Xi , Luo Yanwei , Gui Rong
Published: July 2020

Background Huanglian Jiedu Decoction (HLJDD) is a traditional Chinese prescription for the treatment of influenza, inflammation and other ailments related to heat-syndrome, a typical pathological symptom in Traditional Chinese Medicine. It was recommended as one of the basic prescriptions among the Proposed Diagnoses and Treatment issued by China’s National Health Commission. In this work we investigated the molecular mechanism of action of Huanglian Jiedu Decoction in the treatment of Corona Virus Disease 2019 (COVID-19) through network pharmacology and molecular docking approaches. Methods The chemical constituents and action targets of Coptis chinensis, Scutellaria baicalensis, Phellodendron amurense, Gardenia jasminoides in HLJDD were retrieved on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The database of UniProt and GeneCards were used to query the target genes that corresponding to the active compounds, and then a compound-target network was constructed using Cytoscape 3.7.2. GO database was used to annotate GO functions. Reactome was used to analyze KEGG enrichment pathway, predicting the possible mechanisms of active compounds. DAVID database was used to analysis the tissue enrichment. The main active ingredient is molecularly docked with the SARS-CoV-2, ACE2 and TMPRSS2. Results We screened 84 compounds and obtained 341 corresponding target genes in the network. Gene annotation showed that the targets were involved mainly in 457 biological functions. 306 signaling pathways was enriched, involving chemokine and cytokine signaling pathways that mediate inflammation, interferon-γ signaling pathway, p53 pathway. And the targets mainly distributed in the lung liver and placenta, involving a variety of immune cells, such as T cells, B cells. The molecular docking results showed that core compounds such as beta-sitosterol, stigmasterol and quercetin had high affinity with SARS-CoV-2, ACE2 and TMPRSS2, which was comparable with drugs like abidol used to COVID-19 treatment by. Conclusions The active compounds in HLJDD may have a therapeutic effect on COVID-19 through regulating multiple signal pathways by targeting genes such as VEGF, NOS2, IL6, MMP9, IL10, and TGFB1.
Dietary Intake and Hypertension Risk: A Cross-Sectional Survey Using Data from the China hypertension survey, 2012-2015
Authors: Wu Xingwei , Wu Yu , Yong Zhengping , Hou Zhengyao , Zhang Yueqi , Cai Li , Liu Zhou , Tang Yijia , Tong Rongsheng , Wan Shaoping
Published: July 2020

Background: Available data about the effects of dietary intake on hypertension remains limited and conflicting. The purpose of this study was to assess the correlation between dietary intake and the incidence of hypertension. Methods: The China Hypertension Survey was conducted nationwide, and the data of 19,277 residents from Sichuan was organized, and finally 2,010 samples were selected into this study. Standard food frequency questionnaires were used to collect dietary intake data and physical examinations including blood pressure were performed on site. The subjects were classified into hypertensive group (n=356) and non-hypertensive group (n=1,654). The odds ratio (OR) for the occurrence of hypertension according to the quartiles of the dietary intake was evaluated by multivariable logistic regression. Results: After adjustment for all potential confounding variables, more than 50g of daily egg intake was a risk factor for hypertension prevalence (OR=2.11; 95% CI: 1.34-3.32), and 1.94-3.33g of animal oil intake per day was a protective factor (OR=0.57; 95% CI: 0.37-0.88). Conclusions: Our findings demonstrate a significant positive correlation between eggs above 50g and the risk of hypertension, while 1.94-3.33g of animal oil is negatively correlated with the risk of hypertension, indicating that adherence to a small amount of eggs and an appropriate amount of animal oil intake have beneficial effects on the prevention of hypertension.
Fructooligosaccharides improves growth performance and intestinal epithelium function in weaned pigs exposure to Enterotoxigenic Escherichia coli
Authors: Liu Lei , Chen daiwen , Yu Bing , Heng Yin , Huang Zhiqing , Luo Yuheng , Zheng Ping , Mao Xiangbing , Yu Jie , Luo Junqiu , Yan Hui , He Jun
Published: July 2020

Background

This study was conducted to explore the protective potential of Fructooligosaccharides (FOS) against Enterotoxigenic Escherichia coli (ETEC)-induced inflammation and intestinal injury in weaned pigs.
Methods

Twenty-four weaned pigs were randomly assigned into three groups: (1) non-challenge (CON), (2) ETEC-challenge (ECON), and (3) ETEC challenge + 250 mg/kg FOS (EFOS). On day 19, non-challenged pigs were orally infused with sterilized culture while pigs in other groups were orally infused with ETEC (2.5 × 1010 colony-forming units). After 3 days, pigs were slaughtered for sample collection.
Results

We show that ETEC-challenged significantly reduced average daily gain (ADG); however, FOS improved the ADG (P < 0.05) and apparent digestibility of crude protein (CP), gross energy (GE), and ash in the ETEC-challenged pigs (P < 0.05). FOS reduced plasma concentrations of IL-1β and TNF-α, and elevated the concentrations of immunoglobulin A (IgA) and immunoglobulin M (IgM) (P < 0.05). Interestingly, FOS elevated villus height in duodenum, and elevated the ratio of villus height to crypt depth in the duodenum and ileum in the ETEC-challenged pigs (P < 0.05). Moreover, FOS increased lactase activity in the duodenum and ileum (P < 0.05). The activities of sucrase and alkaline phosphatase (AKP) were higher in EFOS group than in the ECON group (P < 0.05). Importantly, FOS up-regulated the expressions of critical genes in intestinal epithelium function such as zonula occludens-1 (ZO-1), L-type amino acid transporter-1 (LAT1), and cationic amino acid transporter-1 (CAT1) in the duodenum and the expressions of ZO-1 and glucose transporter-2 (GLUT2) in the jejunum (P < 0.05). FOS also up-regulated the expressions of occludin, fatty acid transporter-4 (FATP4), sodium glucose transport protein 1 (SGLT1), and GLUT2 in the ileum (P < 0.05). FOS significantly increased the concentrations of acetic acid, propionic acid and butyric acid in the cecal digesta. Additionally, FOS reduced the populations of Escherichia coli, but elevated the populations of Bacillus and Bifidobacterium in the caecal digesta (P < 0.05).
Conclusions

These results suggested that FOS can improve the growth performance and intestinal health in weaned pigs upon ETEC challenge, which was associated with suppressed inflammatory responses and improved intestinal epithelium functions and microbiota.
High order semi-implicit weighted compact nonlinear scheme for the all-Mach isentropic Euler system
Authors: Jiang Yanqun , Chen Xun , Zhang Xu , Xiong Tao , Zhou Shuguang
Published: July 2020

The computation of compressible flows at all Mach numbers is a very challenging problem. An efficient numerical method for solving this problem needs to have shock-capturing capability in the high Mach number regime, while it can deal with stiffness and accuracy in the low Mach number regime. This paper designs a high order semi-implicit weighted compact nonlinear scheme (WCNS) for the all-Mach isentropic Euler system of compressible gas dynamics. To avoid severe CFL restrictions for low Mach flows, the nonlinear fluxes in the Euler equations are split into stiff and non-stiff components. A third-order implicit-explicit (IMEX) method is used for the time discretization and a fifth-order WCNS is used for the spatial discretization. The designed semi-implicit WCNS is asymptotic preserving and asymptotically accurate in the zero Mach number limit. One- and two-dimensional numerical examples in both compressible and incompressible regimes are given to demonstrate the advantages of the designed method.
Dissecting Molecular Mechanisms Underlying H2O2-induced Apoptosis of Mouse Bone Marrow Mesenchymal Stem Cell: Role of Mst1 Inhibition.
Authors: Zhang Qian , Cheng Xianfeng , Zhang Haizhou , Zhang Tao , Wang Zhengjun , Zhang Wenlong , Yu Wancheng
Published: July 2020

Background
Bone marrow mesenchymal stem cell (BM-MSC) has been shown to treat pulmonary arterial hypertension (PAH). However, excessive reactive oxygen species (ROS) increases the apoptosis of BM-MSCs, leading to poor survival and engraft efficiency. Thus, improving the ability of BM-MSCs to scavenge ROS may considerably enhance the effectiveness of transplantation therapy. Mammalian Ste20-like kinase 1 (Mst1) is a pro-apoptotic molecule which increases ROS production. The aim of this study is to uncover whether Mst1 inhibition enhanced the tolerance of BM-MSCs under H2O2 condition and the underlying mechanisms.
Methods
Mst1 expression in BM-MSCs was inhibited via transfection with adenoviruses expressing a short hairpin (sh) RNA directed against Mst1 (Ad-sh-Mst1) and exposure to H2O2. Cell viability was detected by Cell counting Kit 8 (CCK‑8) assay, and cell apoptosis was analyzed by Annexin V-FITC/PI, Caspase 3 Activity Assay kits, and pro caspase 3 expression. ROS level was evaluated by the ROS probe DCFH-DA, mitochondrial membrane potential (ΔΨm) assay, SOD1/2, CAT, and GPx expression. Autophagy was assessed using transmission electron microscopy, stubRFP-sensGFP-LC3 lentivirus and autophagy-related protein expression. The autophagy/Keap1/Nrf2 signal in H2O2-treated BM-MSC/sh-Mst1 was also measured.
Results
Mst1 inhibition reduced ROS production, increased antioxidant enzyme SOD1/2, CAT, GPx expression, maintained ΔΨm, and alleviated cell apoptosis in H2O2-treated BM-MSCs. In addition, this phenomenon was closely correlated with the autophagy/Keap1/Nrf2 signal pathway. The autophagy inhibitor, the antioxidant pathway Keap1/Nrf2, was also blocked when autophagy was inhibited by 3-MA. However, Keap1 or Nrf2 knockout via siRNA had no effect on autophagy activation or suppression.
Conclusion
Mst1 inhibition mediates the cytoprotective benefit of mBM-MSCs against H2O2 oxidative stress injury. The underlying mechanisms involve autophagy activation and the Keap1/Nrf2 signal pathway.
Micelles Self-Assembled by 3-O-β-D-Glucopyranosyl Latycodigenin Enhance Cell Membrane Permeability, Promote Antibiotic Pulmonary Targeting and Improve Anti-infective Efficacy
Authors: Zhang Man , Ye Lili , Huang Hao , Cheng Dandan , Liu Kaixin , Wu Wenbo , Shen Fukui , Jiang Zhihong , Hou Yuanyuan , Bai Gang
Published: July 2020

Background: Nanoparticle-based pulmonary drug delivery systems are commonly developed and applied for drug-targeted delivery. It exhibits significant advantages compared to traditional pulmonary drug delivery systems. However, developing a formulation for each drug is a time-consuming and laborious task. Results: This study designed and constructed a universal lung-targeting nanoparticle. The self-assembled micelles were composed of a platycodon secondary saponin, 3-O-β-D-glucopyranosyl platycodigenin 682 (GP-682), via its specific amphiphilic structure. GP-682 micelles obtained a relatively stable zeta potential with a particle size between 60 to 90 nm, and the critical micelle concentration (CMC) value was approximately 42.3 μg/mL. Pre-incubation of GP-682 micelles markedly enhanced the cell membrane permeability, and improved drug uptake in vitro. The results were visualized using fluorescent dye tracing, transmission electron microscopy (TEM) observation and lactate dehydrogenase (LDH) releasing assay. The benefits enhanced the distribution of levofloxacin (Lev) in mouse lung tissue and reduced the overdosing of antibiotics. The acute lung injury mice model induced by Pseudomonas aeruginosa PA 14 strain demonstrated that pre-injection of GP-682 micelles before antibiotic administration produced a higher survival rate and anti-infective efficacy in vivo. It included a reduction in pulmonary injury, bacterial invasion and cytokines expression compared to treatment with Lev alone. Conclusions: GP-682 micelles are another nanoparticle-based pulmonary drug delivery system and provides a new option for lung-targeting therapy.
The Circular RNA circZFR Phosphorylates Rb Promoting Cervical Cancer Progression by Regulating the SSBP1/CDK2/cyclin E1 Complex
Authors: Zhou Mingyi , Yang Zhuo , Wang Danbo , Chen Peng , Zhang Yong
Published: July 2020

Background: As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown. Methods: We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change >2, and P <0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR.Results: Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation. Conclusion: Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.
Integrating the lncRNA and mRNA expression profiles of TLR4-primed mesenchymal stem cells in ankylosing spondylitis
Authors: Li Yuxi , Li Ming , Huang Jiajun , Liang Yuwei , Huang Junshen , Liu Xiangge , Cheng Ziying , Lu Shixin , Liu Ting , Huang Lin
Published: July 2020

Background

Our previous study found that the toll-like receptor 4 (TLR4) expression of ankylosing spondylitis (AS) patients was significantly different from that of healthy donors. The goals of this study were to explore the expression profiles and functional networks of lncRNAs and mRNAs in TLR4-primed mesenchymal stromal cells from AS patients (AS-MSCs) and to clarify the mechanisms by which TLR4-primed MSCs exert immunoregulatory effects in AS.
Methods

Firstly, the immunoregulatory effects of MSCs were determined after TLR4 activation. Then, the differentially expressed (DE) lncRNAs and mRNAs between the control group (AS-MSCs without stimulation) and experimental group (AS-MSCs stimulated with lipopolysaccharide) were identified through high-throughput sequencing followed by qRT-PCR confirmation. Finally, bioinformatic analyses were performed to identify the critical biological functions, signalling pathways and associated functional networks involved in the TLR4-primed immunoregulatory function of AS-MSCs.
Results

TLR4-primed AS-MSCs showed a strong ability to inhibit the proliferation of peripheral blood mononuclear cells (PBMCs) with 1 µg/ml LPS stimulation for 4 hours. A total of 147 DE lncRNAs and 698 DE mRNAs were identified between TLR4-primed AS-MSCs and unstimulated AS-MSCs. Significant fold changes in lncRNA and mRNA levels were confirmed by qRT-PCR. GO and KEGG analysis demonstrated that the DE mRNAs and lncRNAs were highly associated with the inflammatory response. Cis-regulation prediction revealed 9 novel lncRNAs while trans-regulation prediction revealed 15 lncRNAs, respectively.
Conclusions

Our research describes the lncRNA and mRNA expression profiles and functional networks in TLR4-primed AS-MSCs, which is supposed to enhance the understanding of the pathogenesis of AS-MSC immunoregulatory dysfunction.
Melphalan induces cardiotoxicity through oxidative stress in cardiomyocytes derived from human induced pluripotent stem cells
Authors: Liu Rui , Li Dong , Sun Fangxu , Rampoldi Antonio , Maxwell Joshua , Wu Ronghu , Fischbach Peter , Castellino Sharon , Du Yuhong , Fu Haian , Mandawat Anant , Xu Chunhui
Published: July 2020

Background: Treatment-induced cardiotoxicity is a leading noncancer-related cause of acute and late onset morbidity and mortality in cancer patients on antineoplastic drugs such as melphalan—increasing clinic case reports have documented that it could induce cardiotoxicity including severe arrhythmias and heart failure. As the mechanism by which melphalan impairs cardiac cells remains poorly understood, here we aimed to use cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) to investigate the cellular and molecular mechanisms of melphalan-induced cardiotoxicity and to explore potential targeted therapeutics.Methods: hiPSC-CMs were generated and treated with clinically relevant doses of melphalan. For the characterization of melphalan-induced cardiotoxicity, cell viability and apoptosis were quantified. Ca 2+ transient and contractility analyses were used to examine the alterations of hiPSC-CM function. Proteomic analysis, reactive oxygen species detection, and RNA-Sequencing were conducted to investigate underlying mechanisms. Results: Melphalan treatment of hiPSC-CMs induced oxidative stress, caused Ca 2+ -handling defects and dysfunctional contractility, altered global transcriptomic and proteomic profiles, and resulted in apoptosis and cell death. The antioxidant N-acetyl-L-cysteine attenuated these genomic, cellular and functional alterations. In addition, several other signaling pathways including the p53 and transforming growth factor-β signaling pathways were also implicated in melphalan-induced cardiotoxicity according to the proteomic and transcriptomic analyses. Conclusions: Melphalan induces cardiotoxicity through the oxidative stress pathway. This study provides a unique resource of the global transcriptomic and proteomic datasets for melphalan-induced cardiotoxicity and can potentially open up new clinical mechanism-based targets to prevent and treat melphalan-induced cardiotoxicity.
Impact of bilateral-coordinated movement on manipulative skill competency in school-aged children
Authors: Chen Jun , Wang Xiaozan , Chen Weiyun
Published: July 2020

Background Researchers found that manipulative skill competency in childhood not only help improve physical activity participation, but also help adolescent learn specialized sport skills. This study aimed at examining the effects of an 8-week bilateral-coordinated movement (BCM) intervention on manipulative skill competency in school-aged children.Methods Participants were 314 fourth-grade students in two elementary schools. This study used 2-arm quasi-experimental research design. For one elementary school, two fourth-grade classes were assigned to the BCM group, the other two fourth-grade classes were assigned to the control group. For another elementary school, one fourth-grade class was assigned to the BCM group and another fourth-grade class to the control group. The students in the BCM group received an 8-week, two 40-minute BCM lessons in soccer and another 8-week, two 40-minute BCM lessons in basketball, while the control group received an 8-week, two 40-minute regular PE lessons in soccer and basketball, respectively. Students’ manipulative skill competency in soccer and basketball skills were pre- and post-tested using the two PE Metric assessment rubrics. Data were analyzed by means of descriptive statistics, independent sample t test, ANCOVA and ANOVA repeated measures.Results The results showed a significant main effect of time (pre-test vs. post-test) in soccer skills (F = 273.095, p = .000, 𝜂2 = .468) and in basketball skills (F = 74.619, p = .000, 𝜂2 = .193). Also, the results revealed a significant main effect of group (BCM group vs. control group) in soccer skills (F = 37.532, p = .000, 𝜂2 = .108), marginal significant main effect of group in basketball skills (F = 3.619, p = .058, 𝜂2 = .011). Further, there was significant interaction effect between the time and group in soccer skills (F = 37.532, p = .000, 𝜂2 = .108) and in basketball skills (F = 18.380, p = .000, 𝜂2 = .056).Conclusions It was concluded that after participated in the 8-week, 16 40-min lessons of BCM, the fourth-grade students had greater improvement in soccer and basketball dribbling, passing and receiving skills, compared to the control group.
Medical Waste Management: An Assessment at District-Level Public Health Facilities in Bangladesh
Authors: Sujon Hasnat , Biswas Taposh Kumar , Chowdhury Aklima , Chowdhury Mahbub Elahi
Published: July 2020

Background Due to the heavy patient-load and various types of services, the public health facilities produce a bulk of medical wastes (MW) in Bangladesh. Improper disposal of MW increases the risk of infection among the healthcare service personnel, patients, and attendants. The current study aimed to assess the practices of MW management and quantify those to find out the gaps in the specific steps of waste management.Methods As part of a larger intervention study, a facility assessment was conducted during November 2015 to March 2016 at a District Hospital (DH) and a Mother and Child Welfare Centre (MCWC) both being located in the same district, Non-participatory observation of MW management was done using a checklist developed following the Guideline for Medical Waste Management of Bangladesh. Scoring was applied for various activities of MW management performed in the study facilities.Results The overall scores in bin management, segregation, and collection of wastes were 64.5%, 58.1%, and 62.0% in the DH and 53.1%, 41.5%, and 48.0% in the MCWC respectively. The performance of operation theatre in MCWC was the lowest among different corners (16.7–36.0%). Re-usable waste was segregated poorly (32% in DH and 0% in MCWC), and almost none was shredded (4% in DH and 0% in MCWC). The wastes were transported from in-house to out-house temporary storage area in open-bin without any trolley or specific route. Storage area was accessible to unauthorized persons, e.g. waste-picker in DH. While DH segregated 84% of its infectious wastes at source, they eventually got mixed-up with other wastes in the storage area and delivered to municipality for dumping. MCWC could segregate only 40% of its infectious wastes at source and disposed those, using pit method. Both the facilities disposed sharp medical wastes by open-air burning and liquid wastes through sewerage without any treatment.Conclusions The performance of MW management was poor in both the study facilities. Advocacy to the healthcare personnel and refresher training, along with supportive supervision and monitoring, may improve the situation. Moreover, larger study is needed to find out the reasons behind such poor MW management.
How does area-level deprivation depress an individual’s self-rated health and life satisfaction? Evidence from a nationwide population-based survey in Japan
Authors: Oshio Takashi , Kimura Hiromi , Nishizaki Toshimi , Omori Takashi
Published: July 2020

Background: Area-level deprivation is well known to have an adverse impact on mortality, morbidity, or other specific health outcomes. This study examined how area-level deprivation may affect self-rated health (SRH) and life satisfaction (LS), an issue that is largely understudied.Methods: We used individual-level data obtained from a nationwide population-based internet survey conducted between 2019–2020, as well as municipality-level data obtained from a database provided by the Japanese government (N=12 461 living in 366 municipalities). We developed multilevel regression models to explain an individual’s SRH and LS scores using four alternative measures of municipality-level deprivation, controlling for individual-level deprivation and covariates. We also examined how health behavior and interactions with others mediated the impact of area-level deprivation on SRH and LS.Results: Participants in highly deprived municipalities tended to report poorer SRH and lower LS. For example, when living in municipalities falling in the highest tertile of municipality-level deprivation as measured by the z-scoring method, SRH and LS scores worsened by a standard deviation of 0.05 (p<0.05) when compared with those living in municipalities falling in the lowest tertile of deprivation. In addition, health behavior mediated between 17.6 % and 33.1 % of the impact of municipality-level deprivation on SRH and LS, depending on model specifications.Conclusion: This study showed that area-level deprivation modestly depressed an individual’s general health conditions and subjective well-being. The results underscore the need for public health policies to improve area-level socioeconomic conditions and to promote healthy lifestyles to alleviate the negative impact of area-level deprivation.
Significance of Coagulation and Fibrinolysis Markers for Benign and Malignant Soft Tissue Tumors
Authors: Asanuma Kunihiro , Nakamura Tomoki , Hagi Tomohito , Okamoto Takayuki , Kita Kouji , Nakamura Koichi , Matsuyama Yumi , Yoshida Keisuke , Asanuma Yumiko , Sudo Akihiro
Published: July 2020

Background: The intimate relationship between coagulation and fibrinolysis in malignant tumors is a well-known phenomena, with the malignant phenotype enhancing coagulation and fibrinolysis. We hypothesized that soft tissue sarcoma (STS) affects the expression of coagulation and fibrinolysis markers, which could be used to distinguish STS from benign soft tissue tumors. We analyzed the correlations between plasma levels of D-dimer (DD), plasmin-α2 plasmin inhibitor complex (PIC), soluble fibrin (SF), and thrombin-antithrombin III complex (TAT) in benign soft tissue tumors and STS to elucidate whether these markers can be used to predict STS.Methods: Plasma DD, PIC, SF and TAT levels in primary soft tissue tumors (benign, 67, STS 68) were measured before biopsy or treatment. The marker levels were analyzed and compared to various clinicopathological parameters.Results: In malignancy (STS), the average DD, PIC and SF levels were significantly higher than in benign tumors. Multivariate logistic analysis of continuous variables indicated that only PIC exhibited a significant difference (OR: 24.5, 95%CI: 3.55-170, p=0.0012). Receiver operating characteristic curve analysis produced area under the curve values for DD: 0.691, PIC: 0.784, SF: 0.734 and TAT: 0.588. Youden’s index was used to establish thresholds of 0.37 (DD), 0.80 (PIC), 0.90 (SF) and 0.82 (TAT). Threshold values for PIC and SF indicated high specificity (0.881, 0.791) and high positive predictive value (0.818, 0.745), respectively The highest accuracy value among the markers was observed for PIC (0.704). Significant differences in multivariate analysis of binary variables were demonstrated by categorizing low and high groups based on their threshold, PIC (≥0.80) (OR: 3.36, 95%CI: 1.19-9.43, p=0.0212) and SF (≥0.90) (OR: 2.63, 95%CI: 1.04-6.66, p=0.0404) . Conclusions: Of the coagulation and fibrinolysis markers studied, increased PIC levels were related to STS and over 0.80 PIC was the most suitable for the prediction of STS, which, along with other diagnostic tools, represents a helpful subsidiary tool for the prediction of STS.
Determination of Localized Skin Temperature of the Transtibial Residual Limb
Authors: Ghoseiri Kamiar , Allami Mostafa , Murphy Justin R. , Page Phil , Button Duane C.
Published: July 2020

Background: Interventions to resolve thermal discomfort as a common complaint in amputees, are usually chosen based on the residual limb skin temperature while wearing prosthesis; whereas, less attention was paid to residual limb skin temperature while outside of the prosthesis. The objective of this study was to explore the localized and regional skin temperature over the transtibial residual limb (TRL) while outside of the prosthesis.Methods: Eight unilateral transtibial amputees were enrolled in this cross sectional study. Participants sat on a chair and rested for 30 minutes while their prosthesis was removed. Twelve sites were marked in four columns (anterolateral, anteromedial, posteromedial, and posterolateral) and three rows (proximal, middle, and distal) over the residual limb and used for attachment of analog thermistors. Skin temperature was recorded and compared during 11 minutes. Furthermore, the relationship of skin temperature with participants’ demographic and clinical characteristics were explored.Results: The middle and distal zones of the anteromedial column had the highest and lowest skin temperatures (29.8 and 26.3°C, p<0.05), respectively. The average temperature of the TRL was 27.73±0.83°C and had no significant relationships (p>0.05) with participants’ demographic and clinical characteristics.Conclusions: An unequal distribution of temperature over the TRL was found with significantly higher and lower temperatures at its anterior column and distal row, respectively. This temperature pattern should be considered for thermoregulation strategies. Further investigation of the residual limb temperature while considering muscles thickness and blood perfusion rate are warranted with and without prosthesis.
hPMSCs protects against aging-induced oxidative damage of CD4+ T cells through activating Akt-mediated Nrf2 antioxidant signaling
Authors: Xiong Yanlian , Wang Yueming , Zhang Jiashen , Zhao Nannan , Zhang Aiping , Zhao Dongmei , Yu Zhenhai , Yin Yancun , Song Lele , Xiong Yanlei , Luan Xiying
Published: July 2020

Background: Mesenchymal stem cells (MSCs) was considered as regenerative therapeutic approach in both acute and chronic diseases. However, whether MSCs regulate the antioxidant metabolism of CD4+ T cells and weaken immunosenescence remains unclear. Here, we reported the protective effects of hPMSCs in aging-related CD4+ T cell senescence and identified the underlying mechanisms using a D-gal induced mouse aging model.Methods: In vivo study, 40 male C57BL/6 mice (8 weeks) were randomly divided into four groups: control group, D-gal group, hPMSC group and PBS group. In in vitro experiment, human naive CD4+ T (CD4CD45RA) cells were prepared using a naive CD4+ T cell isolation kit II and pretreated with the Akt inhibitor LY294002 and Nrf2 inhibitor ML385. Then, isolated naive CD4+ T cell were cocultured with hPMSCs for 72 h in the absence or presence of anti-CD3/CD28 Dynabeads and IL-2 as a mitogenic stimulus. Intracellular ROS changes were detected by flow cytometry. The activities of the antioxidant enzymes superoxide dismutase, glutathione peroxidase and catalase were measured by colorimetric analysis. The senescent T cells were detected SA-β-gal stain. The expression of aging related proteins were detected by Western blotting, RT-PCR and confocal microscopy.Results: We found that hPMSC treatment markedly decreased the ROS level, SA-β-gal positive cells number, senescence-associated secretory phenotype (IL-6 and OPN) expression and aging-related protein (P16 and P21) expression in senescent CD4+ T cells. Furthermore, hPMSC treatment effectively upregulated Nrf2 nuclear translocation and the expression of downstream target genes (HO-1, CAT, GCLC and NQO1) in senescent CD4+ T cells. Moreover, in vitro studies revealed that hPMSCs attenuated CD4+ T cell senescence by upregulating the Akt/GSK-3β/Fyn pathway to activate Nrf2 functions. Conversely, the antioxidant effects of hPMSCs were blocked by the Akt inhibitor LY294002 and Nrf2 inhibitor ML385 in senescent CD4+ T cells.Conclusions: Our results indicate that hPMSCs attenuate D-gal induced CD4+ T cell senescence by activating Nrf2-mediated antioxidant defenses and that upregulation of Nrf2 by hPMSCs is regulated via the Akt/GSK-3β/Fyn pathway.
Comparative evaluation of methods testing in vitro sensitivity to azithromycin in multi-drug resistant Pseudomonas aeruginosa isolated from cystic fibrosis patients
Authors: Soerensen Michael , Nurjadi Dennis , Khakimov Bakhodur , Boutin Sébastien , Dalpke Alexander H. , Eigenbrod Tatjana
Published: July 2020

Long-term treatment with azithromycin is a therapeutic option in Cystic Fibrosis (CF) patients chronically infected with P. aeruginosa . It was recently shown that azithromycin has direct antimicrobial activity when P. aeruginosa isolates are tested in Roswell Park Memorial Institute medium supplemented with fetal calf serum (RPMI 1640/FCS) by broth microdilution. We now investigated whether (i) azithromycin might also be active against multidrug resistant (MDR) P. aeruginosa isolated from CF patients and (ii) how in vitro sensitivity assays perform in synthetic cystic fibrosis sputum medium (SCFM), a medium that mimics the particular CF airway environment. In 17 (59%) out of 29 MDR P. aeruginosa CF isolates MICs for azithromycin ranged between 0.25 and 8 µg/ml and 12 isolates (41%) showed a MIC ≥512 µg/ml when measured in RPMI/FCS. In contrast, MICs were ≥256 µg/ml for all P. aeruginosa MDR isolates when tested in either SCFM or in conventional cation-adjusted Mueller Hinton Broth. High MIC values observed in CF adapted medium SCFM for both PAO1 and MDR P. aeruginosa CF isolates, as opposed to findings in RPMI, argue against routine azithromycin MIC testing of CF isolates.
Regulatory T cells promote glioma cell stemness through TGF-β–NF-κB–IL6–STAT3 signaling
Authors: Liu Shasha , Zhang Chaoqi , Wang Boqiao , Zhang Huanyu , Li Congcong , Qin Guohui , Cao Ling , Gao Qun , Ping Yu , Zhang Kai , Lian Jingyao , Zhao Qitai , Wang Dan , Zhang Zhen , Zhao Xuan , Yang Li , Huang Lan , Yang Bo , Zhang Yi
Published: July 2020

Background: Glioma stem cells (GSCs) contribute to the malignant growth of glioma, but little is known about the interaction between GSCs and the tumor microenvironment (TME). The aim of this study was to examine how regulatory T cells (Tregs) increase the stemness and tumorigenic potential of glioma cells.Methods: Tumor and peripheral blood samples were collected during surgery from 86 patients with glioma, and 75 samples of adjacent noncancerous tissue were collected, and Regulatory T cells (Tregs) were extracted from blood. Cytological and histochemical analyses were conducted to examine the mechanisms of Treg action on cancer cells. A mouse glioma model was used.Results: Intense infiltration by Tregs facilitated the qualities of GSCs through TGF-β secretion, which helped to coordinate tumor growth. Mechanistic investigations indicated that TGF-b acted on cancer cells to induce expression of the core cancer stem cell-related genes ( CD133, SOX2, NESTIN, MUSASHI1, and ALDH1A ) and to induce sphere formation via the NF-κB–IL6–STAT3 signaling pathway, resulting in increased cancer stemness and tumorigenic potential. Tregs promoted glioma tumor growth, and this effect was abrogated by blockade of the IL6 receptor by tocilizumab, which also demonstrated some therapeutic efficacy in a xenograft model. Expression levels of CD133, IL6 and TGF-β were found to serve as prognostic markers for glioma.Conclusions: Our findings reveal a new immune-associated mechanism underlying Treg-induced GSCs. Efforts to target this network may provide an effective strategy for treating glioma.
Optimal Timing of Ureteroscopic Lithotripsy after the Initial Drainage Treatment and Risk Factors for Postoperative Febrile Urinary Tract Infection in Patients with Obstructive Pyelonephritis: A Retrospective Study
Authors: Itami Yoshitaka , Miyake Makito , Owari Takuya , Iwamoto Takashi , Gotoh Daisuke , Momose Hitoshi , Fujimoto Kiyohide , Hirao Shuya
Published: July 2020

Background: A history of preoperative obstructive pyelonephritis has been reported as a risk factor for febrile urinary tract infection (fUTI) after ureteroscopic lithotripsy (URSL). But there is no clear evidence of risk factors for developing fUTI including the optimal timing of URSL after obstructive pyelonephritis treatment.Methods: Of the 1361 patients, who underwent URSL at our hospital from January 2011 to December 2017, 239 patients had a history of pre-URSL obstructive pyelonephritis. The risk factors were analyzed by comparing the patients’ backgrounds with the presence or absence of fUTI after URSL. The factors examined were age, gender, body mass index, comorbidity, presence or absence of preoperative ureteral stent, stone position, stone laterality, stone size, Hounsfield unit (HU) value on computed tomography scan, history of systemic inflammatory response syndrome (SIRS) during obstructive pyelonephritis, period from antipyresis to URSL, ureteral stenting period, operation time, and presence or absence of access sheath at URSL. In addition, the stone components and renal pelvic urinary culture bacterial species during pre-URSL pyelonephritis were also examined.Results: Post-URSL fUTI developed in 32 of 239 patients (13.4%), and 11 of these 32 cases led to SIRS (34.4%). Univariate analysis showed that stone position, stone maximum HU value, presence of SIRS during obstructive pyelonephritis, period from antipyresis to URSL, pre-URSL ureteral stent placement, operation time were risk factors of fUTI. Stone components and urinary cultures during pyelonephritis were not associated with risk of fUTI. Multivariate analysis showed that renal stone position, pre-URSL ureteral stent placement > 21 days, and operation time > 75 minutes were independent risk factors of fUTI following the URSL.Conclusions: F-UTI following the URSL could be avoided by ureteral stent placement period 21 days or less and operation time 75 minutes or less in patients with obstructive pyelonephritis.