bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shexiang Baoxin Pills Inhibited Proliferation and Migration of Human Coronary Artery Smooth Muscle Cells via PI3K/AKT/mTOR Pathway
Authors: Hua Lei , Zhou Yaqing , Hou Can , Chen Jiaxin , Wang Yanjun , Zhang Sheng , Zhou Hanxiao , He Shu , Jia Enzhi 
Published: August 2021

Background: Proliferation and migration of smooth muscle cells in the coronary artery contribute to the deterioration of coronary artery disease (CAD).Aim: This research was designed to study the function of Shexiang Baoxin pills (SBPs) on the proliferation and migration of human coronary artery smooth muscle cells (HCASMCs) and their mechanism.Methods: Oxidized low-density lipoprotein (ox-LDL) was applied to stimulate the proliferation and migration of HCASMCs. The function of ox-LDL and SBP on HCASMCs was evidenced by the cell counting kit-8 assay, cell cycle, and Transwell assay. Network pharmacology was employed to predict the potential targets and pathways of SBP on CAD. Western blot assay and molecular docking were conducted to validate the potential targets and pathways.Results: The current research revealed that 2.5 mg/L SBP significantly inhibited the proliferation and migration of HCASMCs. Besides, network pharmacology revealed 11 candidate targets. Molecular docking and Western blot assay validated that the activation of the top 2 targets STAT3 and MAPK14 was associated with the inhibition of HCASMCs. Moreover, the Western blot assay also detected that HCASMCs treated with ox-LDL promoted the phosphorylation of the PI3K/AKT/mTOR pathway, and SBP inhibited the activation of the PI3K/AKT/mTOR pathway in HCASMCs stimulated by ox-LDL.Conclusion: This study demonstrated that the treatment of CAD using SBP may result from the suppression of the proliferation and migration of HCASMCs. The mechanism of this function partly resulted from relieving the phosphorylation of targets STAT3 and MAPK14 and the PI3K/AKT/mTOR pathway. This study enhanced our comprehension of SBP and provides new targets for the treatment of CAD.
Anti-inflammatory Therapies for Coronary Heart Disease: A Systematic Review and Meta-Analysis
Authors: Wang Haiming , Jiang Min , Li Xin , Zhao Yunzhang , Shao Junjie , Liu Zifan , Lin Lejian , Xu Qiang , Wang Lin , Lu Xuechun , Zhang Haomin , Chen Yundai , Zhang Ran 
Published: August 2021

Background: Anti-inflammatory therapy has been proposed as a promising treatment for coronary heart disease (CHD) that could reduce residual inflammation risk (RIR) and therefore major adverse cardiovascular events. We implemented a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the clinical benefits of anti-inflammatory agents in patients with CHD based on secondary cardiovascular prevention.Methods: We systemically searched the PubMed, Embase, and Cochrane Library databases for RCTs (published between Jan 1, 1950, and June 1, 2021; no language restrictions) that focused on anti-inflammatory therapy for coronary heart disease. Our primary end points of interest were a composite of all-cause death, recurrent myocardial infarction and stroke. We processed pooled data using a random-effects model.Results: Of 1497 selected studies, 18 studies with 67,449 participants met our inclusion criteria and were included in the present meta-analysis. Comparing anti-inflammatory agents with placebo, there was no significant decrease in risk of primary end points, secondary end points, all-cause mortality, cardiac mortality, recurrent myocardial infarction, stroke or revascularization. Further subgroup analysis indicated that anti-inflammatory agents led to a significant reduction in secondary end points (OR 0.87, CI 0.77–0.99; P = 0.03), recurrent myocardial infarction (OR 0.86, CI 0.78–0.95; P = 0.003) and revascularization (OR 0.81, CI 0.70–0.92; P = 0.001) in patients with stable CHD compared with placebo. Moreover, stable CHD patients had a lower propensity for recurrent myocardial infarction than acute coronary syndrome (ACS) patients when using anti-inflammatory agents (P = 0.03). The colchicine subgroup analysis showed that colchicine yielded a promising reduction in the primary end points (OR 0.81, CI 0.70–0.95; P = 0.009) compared with placebo. Anti-inflammatory agents were associated with a higher risk of infection (OR 1.13, CI 1.03–1.23; P = 0.007) and negligible effects on cancers (OR 0.98, CI 0.90–1.06; P = 0.61).Conclusion: Anti-inflammatory agents appear to have beneficial effects in reducing the risk of recurrent myocardial infarction in patients with stable CHD, albeit at the cost of increased infection. Notably, colchicine demonstrates a promising cardioprotective effect with a lower incidence of major cardiovascular events and thus is a potential therapeutic strategy for stable CHD patients.Systematic Review Registration: PROSPERO, identifier CRD42021245514.
A Bibliometric Analysis of Exosomes in Cardiovascular Diseases From 2001 to 2021
Authors: Ma Dan , Guan Baoyi , Song Luxia , Liu Qiyu , Fan Yixuan , Zhao Lin , Wang Tongxin , Zhang Zihao , Gao Zhuye , Li Siming , Xu Hao 
Published: August 2021

Background: Exosomes in cardiovascular diseases (CVDs) have become an active research field with substantial value and potential. Nevertheless, there are few bibliometric studies in this field. We aimed to visualize the research hotspots and trends of exosomes in CVDs using a bibliometric analysis to help understand the future development of basic and clinical research.Methods: The articles and reviews regarding exosomes in the CVDs were culled from the Web of Science Core Collection, and knowledge maps were generated using CiteSpace and VOSviewer software.Results: A total of 1,039 articles were included. The number of exosome articles in the CVDs increased yearly. These publications came from 60 countries/regions, led by the US and China. The primary research institutions were Shanghai Jiao Tong University and Nanjing Medical University. Circulation Research was the journal and co-cited journal with the most studies. We identified 473 authors among which Lucio Barile had the most significant number of articles and Thery C was co-cited most often. After analysis, the most common keywords are myocardium infarction, microRNA and mesenchymal stem cells. Ischemic heart disease, pathogenesis, regeneration, stem cells, targeted therapy, biomarkers, cardiac protection, and others are current and developing areas of study.Conclusion: We identified the research hotspots and trends of exosomes in CVDs using bibliometric and visual methods. Research on exosomes is flourishing in the cardiovascular medicine. Regenerative medicine, exosome engineering, delivery vehicles, and biomarkers will likely become the focus of future research.
Improving Geospatial Agreement by Hybrid Optimization in Logistic Regression-Based Landslide Susceptibility Modelling
Authors: Sun Deliang , Wen Haijia , Xu Jiahui , Zhang Yalan , Wang Danzhou , Zhang Jialan 
Published: August 2021

This study aims to develop a logistic regression model of landslide susceptibility based on GeoDetector for dominant-factor screening and 10-fold cross validation for training sample optimization. First, Fengjie county, a typical mountainous area, was selected as the study area since it experienced 1,522 landslides from 2001 to 2016. Second, 22 factors were selected as the initial conditioning factors, and a geospatial database was established with a grid of 30 m precision. Factor detection of the geographic detector and the stepwise regression method included in logistic regression were used to screen out the dominant factors from the database. Then, based on the sample dataset with a 1:10 ratio of landslides and nonlandslides, 10-fold cross validation was used to select the optimized sample to train the logistic regression model of landslide susceptibility in the study area. Finally, the accuracy and efficiency of the two models before and after screening out the dominant factors were evaluated and compared. The results showed that the total accuracy of the two models was both more than 0.9, and the area under the curve value of the receiver operating characteristic curve was more than 0.8, indicating that the models before and after screening factor both had high reliability and good prediction ability. Besides, the screened factors had an active leading role in the geospatial distribution of the historical landslide, indicating that the screened dominant factors have individual rationality. Improving the geospatial agreement between landslide susceptibility and actual landslide-prone by the screening of dominant factors and the optimization of the training samples, a simple, efficient, and reliable logistic-regression–based landslide susceptibility model can be constructed.
The Temporal-Spatial Variations and Potential Causes of Dust Events in Xinjiang Basin During 1960–2015
Authors: Mu Lamei , Su Jing , Mo Xinyue , Peng Nan , Xu Ying , Wang Meihua , Wang Jinyan 
Published: August 2021

Dust events not only cause local ecosystem degradation and desertification, but also have profound impacts on regional and global climate system, as well as air quality and human health. Dust events in Xinjiang Basin, as the important dust source of Eastern Asia, have undergone a significant change under the global warming background and may be in a new active period after 2000, which is worthy of study. This study provides the temporal and spatial variations of dust events in the Xinjiang Basin based on surface meteorological station observation data during 1960–2015. The results show that Southern Xinjiang is the main dust occurrence region where dust events are significantly more than that in the Northern Xinjiang, and each year more than 73% of dust events occurred in spring and summer. The dust index (DI), which is defined to represent the large-scale variation of dust event, shows a significant downward trend during the past 56 years with a linear decreasing rate −8.2 years−1in Southern Xinjiang. The DI is positively correlated to surface wind speed with a mean correlation coefficient of 0.79. The declining trend of surface wind speed could explain dust events variation during 1960–2000. But in the new active period after 2000, the increase of DI is not consistent with the rising wind speed with the correlation coefficient decreasing to 0.34. It is found that, compared with 1960–1999, the average annual precipitation and frequency increased by 17.4 and 13% during 2000–2015, respectively, and the NDVI also increased at the same time, which indicates that the surface condition changes induced by the increase of precipitation might suppress the occurrence of dust. Moreover, the analysis of high-altitude wind field shows that the variation of the East Asian general circulation’s intensity, dominating the upper-level wind fields in the Xinjiang basin, will change the surface wind speed and precipitation, and further affect the occurrence of dust events.
A Multiplex Thyroid-Specific Assay for Quantification of Circulating Thyroid Cell-Free RNA in Plasma of Thyroid Cancer Patients
Authors: Yang Samantha Peiling , Koh Lian Chye Winston , Kong Kiat Whye , Parameswaran Rajeev , Loke Kelvin Siu Hoong , Ngiam Kee Yuan , Tan Wee Boon , Loh Thomas , Ng David Chee Eng , Goh Boon Cher , Ngeow Joanne , Tai E. Shyong 
Published: August 2021

BackgroundThe standard of care for thyroid cancer management is thyroidectomy and adjuvant radioactive iodine (RAI). There is a paucity of clinical tool that quantifies residual thyroid volume reliably for precise adjuvant RAI dosing. Serum thyroglobulin (TG), tumour marker for thyroid cancer, takes 4 weeks for complete clearance due to its long half-life, and might be undetectable in 12% of structural disease patients. It detects recurrence with a sensitivity of 19–40%, mainly attributed to issue of TG antibody interference with TG immunometric assay. We hypothesise that the quantity of thyroid-specific cell-free RNA (cfRNA) is indicative of amount of thyroid tissues, and that during thyroid surgery, cfRNA levels decrease accordingly.MethodsWe identified 11 biologically significant and highly expressed thyroid-specific targets from Human Protein Atlas and literature. To assess for a fall in thyroid-specific cfRNA level, we recruited 16 patients undergoing thyroid surgery or RAI for malignant or benign thyroid disease, and tracked longitudinal trend of cfRNA. To assess the utility of cfRNA in detecting metastatic thyroid cancer, cfRNA of 11 patients at intermediate to high risk of recurrence was measured during surveillance and at time of clinical recurrence.ResultsThe multiplex assay was capable of amplifying and quantifying multiple thyroid-specific genes in a single reaction. The selected targets were amplified successfully from RNA extracted directly from the thyroid (positive control), indicating that they were highly expressed within thyroid tissue. These cfRNAs were present in plasma, in amounts quantifiable using qRT-PCR. Four cfRNA transcripts (TPO, GFRA2, IVD, TG) fell post-treatment in more than 50% of cohort. The thyroid peroxidase (TPO) cfRNA fell post-therapy in 63% of cohort by 80%, as early as 1 day post-treatment, supporting the potential role as early indicator of remnant thyroid tissue volume. We demonstrated the clinical relevance of circulating TPO cfRNA by tracking temporal changes in setting of peri-treatment, recurrence, and TG Ab positive state.ConclusionUsing a multiplex pre-amplification approach, the TPO cfRNA was a potential biomarker that can track residual thyroid mass. It can be further optimised for quantification of thyroid volume to guide RAI doses and for detection of thyroid cancer recurrence.
Efficiency and Safety of the Selective Relaxant Binding Agent Adamgammadex Sodium for Reversing Rocuronium-Induced Deep Neuromuscular Block: A Single-Center, Open-Label, Dose-Finding, and Phase IIa Study
Authors: Zhao Yanhua , Chen Sifan , Huai Xiaorong , Yu Zhangjie , Qi Youmiao , Qing Jie , Yu Weifeng , Su Diansan 
Published: August 2021

Background: Rapid reversal of neuromuscular block after surgery and anesthesia is often necessary. Here, we reported the primary efficacy and safety data from a phase IIa study on adamgammadex sodium, a newly developed modified γ-cyclodextrin derivative.Methods: This was a phase IIa, single-center, randomized, open-label, and dose-finding study that enrolled 35 patients under general anesthesia who received the neuromuscular blocking agent rocuronium for induction and maintenance of neuromuscular blockade. The subjects were randomized to one of the five adamgammadex dose groups (2, 4, 6, 8, and 10 mg kg−1) and to the 4 mg kg−1 sugammadex group. Pharmacological efficacy was the recovery time from the start of adamgammadex or sugammadex administration to train-of-four (TOF) ratio ≥0.9, 0.8, and 0.7 among the different dose groups. Adverse events were recorded throughout the study.Results: The efficacy in reversing deep neuromuscular block was the same between 4 mg kg−1 sugammadex and adamgammadex. However, in the lowest dose groups of 2 and 4 mg kg−1 adamgammadex, adequate reversal could not be achieved in all subjects. The recovery time of TOF ratio to 0.9, 0.8, and 0.7 was shorter in the adamgammadex 10 mg kg−1 group than in the sugammadex 4 mg kg−1 group. The average values of the TOF ratio after 3 min of administration of adamgammadex 8 and 10 mg kg−1 and sugammadex 4 mg kg−1 were &gt;90%. There were no serious adverse events after the use of adamgammadex, and no subjects had to be withdrawn from the trial.Conclusions: Adamgammadex enabled quick, predictable, and tolerable reversion of rocuronium-induced deep neuromuscular block in a dose-dependent manner. Adamgammadex doses of 6–10 mg kg−1 might be the recommended dose range for further exploration of efficacy. Clinical Trial Registration: This study was registered at chictr.org.cn, identifier: ChiCTR2000038391.
Diagnostic Classification of Bruch's Membrane Opening-Minimum Rim Width and Retinal Nerve Fiber Layer Thickness in Myopic Eyes by Optical Coherence Tomography
Authors: Wang Geng , Zhen Miaoru , Liu Shasha , Qiu Kunliang , Liu Cui , Wang Ji , Zhang Mingzhi 
Published: August 2021

Purpose: This study was conducted in order to compare the diagnostic classification of Bruch's membrane opening-minimum rim width (BMO-MRW) and RNFL thickness in normal myopic subjects by using optical coherence tomography (OCT).Methods: This cross-sectional study involved 75 healthy myopic subjects [spherical equivalent (SE) ≤ −0.5D] from April 2019 to January 2020. One eye of each subject was randomly selected for examination. BMO-MRW and peripapillary RNFL thickness were measured by spectral-domain OCT (Spectralis, Heidelberg Engineering GmbH, Heidelberg, Germany). All the subjects were divided into three groups: low myopic group (SE &gt; −3D), moderate myopic group (−6D &lt; SE ≤ −3D), and high myopic group (SE ≤ −6D). A nonparametric test was used to analyze the difference among groups. Linear regression was used to analyze the relationship between BMO-MRW/RNFL thickness and axial length/spherical equivalent. McNemar test was used to compare the diagnostic classification between BMO-MRW and RNFL thickness.Results: The RNFL thickness classified a significantly higher percentage of eyes as outside normal limits/borderline in at least 1 quadrant (BMO-MRW, 4%; RNFL thickness, 34.67%; p &lt; 0.01). There was no significant correlation between BMO-MRW/RNFL thickness and AL/SE. The low myopia (SE &gt; −3D) had a significantly lower percentage of eyes classified as outside normal limits/borderline in at least 1 quadrant than the moderate myopia (−6D &lt; SE ≤ −3D) and high myopia (SE ≤ −6D) (low myopia, 12.5%; moderate/high myopia, 42.42%/50%; p &lt; 0.05).Conclusion: BMO-MRW had a lower percentage of eyes classified as outside normal limits/borderline in at least 1 quadrant than RNFL thickness in normal myopic subjects. When referring to the diagnostic classification of RNFL thickness in myopic subjects, caution should be exercised in interpreting positive results. Further studies are needed to compare the diagnostic accuracy of these two measurements in myopic glaucoma patients.
Urinary 8-OxoGsn as a Potential Indicator of Mild Cognitive Impairment in Frail Patients With Cardiovascular Disease
Authors: Yao Si-Min , Zheng Pei-Pei , He Wei , Cai Jian-Ping , Wang Hua , Yang Jie-Fu 
Published: August 2021

Oxidative RNA damage has been found to be associated with age-related diseases and 8-oxo-7,8-dihydroguanosine (8-oxoGsn) is a typical marker of oxidative modification of RNA. Urine tests are a feasible non-invasive diagnostic modality. The present study aimed to assess whether the measurement of urinary 8-oxoGsn could represent a potential early maker in mild cognitive impairment (MCI) of frail patients with cardiovascular disease (CVD). In this cross-sectional study performed in China from September 2018 to February 2019. Urinary 8-oxoGsn was measured in frail (Fried phenotype: 3–5) in patients with CVD and was adjusted by urinary creatinine (Cre) levels. Cognitive function was assessed by the Chinese version of the Mini-Mental State Examination (MMSE) and participants were classified into non-MCI (≥24) and MCI (&lt;24) groups. Univariate and multivariate logistic regression models were used to determine the relationship between 8-oxoGsn/Cre and MCI. Receiver operating characteristic (ROC) curve analysis was used to assess the 8-oxoGsn/Cre ratio in relation to MCI in frail patients with CVD. A total of 106 elderly patients were enrolled in this study. The mean age of participants was 77.9 ± 6.8 years, the overall prevalence of MCI was 22.6% (24/106), and 57.5% (61/106) of participants were women. In the multivariate logistic regression analysis, urinary 8-oxoGsn/Cre was independently associated with MCI (odds ratio [OR] = 1.769, 95% confidence interval [CI] = 1.234–2.536, P = 0.002), after adjusting for age, sex, education level, marital status, and serum prealbumin levels. The area under the ROC curve was 0.786 (0.679–0.893) (P &lt; 0.001), and the optimal cut-off value was 4.22 μmol/mol. The urinary 8-oxoGsn/Cre ratio showed a sensitivity of 87.5% and a specificity of 69.5%. The present study suggests the urinary 8-oxoGsn/Cre ratio may be a useful indicator for the early screening of MCI in frail patients with CVD.Clinical Trial RegistrationChiCTR1800017204; date of registration: 07/18/2018. URL: http://www.chictr.org.cn/showproj.aspx?proj=28931.
Cognitive Trajectories and Dementia Risk: A Comparison of Two Cognitive Reserve Measures
Authors: Gallo Federico , Kalpouzos Grégoria , Laukka Erika J. , Wang Rui , Qiu Chengxuan , Bäckman Lars , Marseglia Anna , Fratiglioni Laura , Dekhtyar Serhiy 
Published: August 2021

Background and ObjectivesCognitive reserve (CR) is meant to account for the mismatch between brain damage and cognitive decline or dementia. Generally, CR has been operationalized using proxy variables indicating exposure to enriching activities (activity-based CR). An alternative approach defines CR as residual variance in cognition, not explained by the brain status (residual-based CR). The aim of this study is to compare activity-based and residual-based CR measures in their association with cognitive trajectories and dementia. Furthermore, we seek to examine if the two measures modify the impact of brain integrity on cognitive trajectories and if they predict dementia incidence independent of brain status.MethodsWe used data on 430 older adults aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen, followed for 12 years. Residual-based reserve was computed from a regression predicting episodic memory with a brain-integrity index incorporating six structural neuroimaging markers (white-matter hyperintensities volume, whole-brain gray matter volume, hippocampal volume, lateral ventricular volume, lacunes, and perivascular spaces), age, and sex. Activity-based reserve incorporated education, work complexity, social network, and leisure activities. Cognition was assessed with a composite of perceptual speed, semantic memory, letter-, and category fluency. Dementia was clinically diagnosed in accordance with DSM-IV criteria. Linear mixed models were used for cognitive change analyses. Interactions tested if reserve measures modified the association between brain-integrity and cognitive change. Cox proportional hazard models, adjusted for brain-integrity index, assessed dementia risk.ResultsBoth reserve measures were associated with cognitive trajectories [β × time (top tertile, ref.: bottom tertile) = 0.013; 95% CI: –0.126, –0.004 (residual-based) and 0.011; 95% CI: –0.001, 0.024, (activity-based)]. Residual-based, but not activity-based reserve mitigated the impact of brain integrity on cognitive decline [β (top tertile × time × brain integrity) = –0.021; 95% CI: –0.043, 0.001] and predicted 12-year dementia incidence, after accounting for the brain-integrity status [HR (top tertile) = 0.23; 95% CI: 0.09, 0.58].InterpretationThe operationalization of reserve based on residual cognitive performance may represent a more direct measure of CR than an activity-based approach. Ultimately, the two models of CR serve largely different aims. Accounting for brain integrity is essential in any model of reserve.