Publications by authors named "Xiaoling Yuan"

80 Publications

Grip training improves handgrip strength, cognition, and brain white matter in minor acute ischemic stroke patients.

Clin Neurol Neurosurg 2021 Aug 13;209:106886. Epub 2021 Aug 13.

Department of Neurology, Liaocheng People's Hospital, Liaocheng 252000, China. Electronic address:

Objective: A large proportion of stroke patients experience cognitive impairment. Previous studies found that handgrip training can improve cognitive dysfunction after stroke through an unknown mechanism. In this study, we aimed to examine the influence of handgrip training on the cognition of patients with acute mild ischemic stroke and explore the mechanism using an advanced post-processing method for magnetic resonance imaging.

Methods: Seventy-six patients with acute mild ischemic stroke were recruited for this study and randomly divided into a grip training group (n = 37) and a control group (n = 39). Both groups of patients also received standardized treatment for stroke in the acute phase and for secondary prevention, as well as conventional physical therapy after stroke. Grip strength, global cognitive function, and the local and global efficiencies of white matter networks derived from diffusion tensor images were measured before and after the 12-week training period.

Results: In the within-group comparisons, grip training significantly improved the grip strength (3.52 [3.09-3.96], p = 0.02), Montreal Cognitive Assessment (MoCA) (2.27 [1.68-2.86], p = 0.05), and local, but not global, efficiency of the brain white matter network (0.03 [0.02-0.03], p = 0.02) in the experimental group. In contrast, these parameters were not statistically different over the same period in the control group. In the between-groups comparisons, the improvement of grip strength (2.71 [2.20-3.21], p = 0.01), MoCA (1.17 [0.39-1.95], p = 0.05), and local efficiency (0.02 [0.01-0.03], p = 0.01) showed statistically significant differences after the intervention, but not the absolute value of them, neither at the base line nor after the intervention.

Conclusions: Our results indicate that grip training can improve cognitive function by increasing the local efficiency of brain white matter connectivity. This suggests that white matter remodeling is a potential physiological mechanism connecting grip training and cognition improvement.
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http://dx.doi.org/10.1016/j.clineuro.2021.106886DOI Listing
August 2021

What drives green development in China: public pressure or the willingness of local government?

Environ Sci Pollut Res Int 2021 Aug 22. Epub 2021 Aug 22.

School of Economics and Finance, Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, People's Republic of China.

With China already committing to peak carbon dioxide emissions before 2030 and achieving carbon neutrality before 2060, green development is urgent. It is necessary to clarify the driving mechanism of green development to design the path of green development scientifically. From the internal perspective of the green development system, this paper divides the green development power into external power and internal power. The external power is the political pressure formed by the public's green demands. The internal power is the endogenous power of green development transformed by the political promotion willingness of local government leaders. The research shows that (1) the green demands from the public and the accompanying political pressure can form the driving force of green development. (2) The political promotion intention has not been transformed into the endogenous driving force to promote green development in the research period. (3) The external driving force of public appeal is closely related to economic development, income and consumption levels, and education. This paper enriches the research literatures on the driving mechanism of green development and provides theoretical and practical exploration for the driving path of green development.
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http://dx.doi.org/10.1007/s11356-021-16059-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380190PMC
August 2021

Effectiveness of omalizumab in patients with severe allergic asthma: A retrospective study in China.

Respir Med 2021 Jun 29;186:106522. Epub 2021 Jun 29.

Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background: We conducted the first real-world study of treatment with omalizumab, a humanized monoclonal anti-immunoglobulin E antibody, in Chinese patients with severe allergic asthma.

Objective: The primary objective was the steroid-sparing effect of omalizumab after 12 and 16 weeks of treatment. Characteristics of the patient population, treatment patterns, response rate, and other measures of therapeutic effectiveness were also reported.

Methods: This nationwide, retrospective, real-world study was conducted in patients with severe allergic asthma who were treated with omalizumab in China. Data, including demographics, Asthma Control Test (ACT) and laboratory and lung function test results, and omalizumab use information, were extracted from patient records collected as part of a previously conducted real-world survey (Asthma Group of the Respiratory Disease Society of the Chinese Medical Association).

Results: In total, 139 patient records were included; 131 and 118 patients remained on treatment at the ≥12- and ≥16-week time points, respectively. The mean ± standard deviation age and median asthma duration (interquartile range) were 47.4 ± 14.3 and 7 (4, 15) years, respectively; 75.6% of patients had a history of allergic disease. Reductions (versus baseline) in inhaled corticosteroid/long-acting β2 agonists or oral corticosteroids were reported in 61.1% and 63.6% of patients at ≥12 and ≥ 16 weeks, respectively. There were significant improvements in ACT scores (6.08, P < .001) and nitric oxide fraction in exhaled air (-13.0, P = .01) from baseline. Multivariate analysis revealed that age and allergic medical history were predictors of omalizumab treatment response. No serious adverse events were reported.

Conclusion: Real-world omalizumab treatment was efficacious and well-tolerated in Chinese patients with severe allergic asthma.
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http://dx.doi.org/10.1016/j.rmed.2021.106522DOI Listing
June 2021

Tectochrysin ameliorates murine allergic airway inflammation by suppressing Th2 response and oxidative stress.

Eur J Pharmacol 2021 Jul 18;902:174100. Epub 2021 Apr 18.

Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225009, China; Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou University Medical College, Yangzhou, 225009, China; Xinghua People's Hospital, Yangzhou University, Xinghua, Jiangsu, 225700, China. Electronic address:

Tectochrysin, a flavonoid compound, can be isolated from propolis, Alpinia oxyphylla Miq, and Lychnophora markgravii. This study evaluated the efficacy of tectochrysin in the treatment of shrimp tropomyosin (ST)-induced mouse asthma. Mice were sensitized with intraperitoneal (i.p.) injection of ST together with aluminum hydroxide as an adjuvant to establish a mouse model of asthma. Mice were i.p.-treated daily with tectochrysin. IgE levels in plasma, Th2 cytokines from both bronchoalveolar lavage (BAL) fluid and splenocytes, and CD200R on basophils in peripheral blood were measured. Histological analyses of lung tissues and accumulation of leukocytes in BAL fluid were performed. Lung eosinophil peroxidase, catalase and glutathione peroxidase activities were examined. ST was found to markedly increase eosinophilic inflammation and Th2 response in mice. Tectochrysin treatment reduced the level of IgE in plasma, the percentage of eosinophils in total white blood cells in peripheral blood, the total number of cells in BAL fluid, and eosinophil peroxidase activity in lung tissues. Tectochrysin attenuated ST-induced infiltration of eosinophils and epithelial mucus secretion in lung tissues and suppressed the overproduction of Th2 cytokines (IL-4 and IL-5) in BAL fluid. Tectochrysin also attenuated Th2 cytokine (IL-4 and IL-5) production from antigen-stimulated murine splenocytes in vitro, decreased the expression of CD200R on basophils in peripheral blood of asthmatic mice and inhibited IL-4 secretion from IgE-sensitized RBL-2H3 cells. In addition, tectochrysin enhanced catalase and glutathione peroxidase activities in lung tissues. Our findings demonstrate that TEC ameliorates allergic airway inflammation by suppressing Th2 response and oxidative stress.
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http://dx.doi.org/10.1016/j.ejphar.2021.174100DOI Listing
July 2021

The Changing Patterns of Consumers' Behavior in China: A Comparison during and after the COVID-19 Pandemic.

Int J Environ Res Public Health 2021 03 2;18(5). Epub 2021 Mar 2.

School of Economics and Finance, Xi'an Jiaotong University, Xi'an 710061, China.

This paper has an opportunity to collect questionnaire-based data regarding respondents' life choices in China at the peak of COVID-19 outbreak (i.e., around 9-11 March 2020) and in a relatively stable period where the national pandemic was over and the lockdown policy was halted (i.e., around 25-30 March 2020). Comparing respondents' answers about their most fundamental aspects of life during and after the pandemic, including income level, expenditure structure and level, purchase method, study method, food price and quality, and dining habit, both the descriptive and econometric models reveal that Chinese consumers' life patterns were not significantly changed. These findings may imply a "new normal" where consumers stick to their new living habits that were forged during the pandemic. Therefore, policy makers have to envisage such an implicative socio-economic change (cost) brought by the implementation of a lock down policy in a long run, in addition to direct and explicit economic losses. However, improving food quality and controlling food price appear to be the strong and stable safety signals to reassure consumers in this complicated environment.
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http://dx.doi.org/10.3390/ijerph18052447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967584PMC
March 2021

The objects, agents, and tools of Chinese co-governance on air pollution: a review.

Environ Sci Pollut Res Int 2021 May 26;28(20):24972-24991. Epub 2021 Mar 26.

School of International Business, Shaanxi Normal University, Xi'an, 710119, China.

The social and economic development in China has not only made a series of great achievements but also suffered from increasingly serious air pollution. It is of great significance to explore the co-governance mechanism of air pollution in order to promote high-quality development and the construction of "beautiful China." Based on an analysis using the concept of co-governance, this paper reviews the research from four aspects: the multi-object relationships, multi-agent framework, and the co-governance technical tools and policy tools. The results show that the current research has many deficiencies: a lack of research on the size, direction, and driving factors of the correlation of objects; the construction of the multi-agent framework focused only on concepts and lacking the design of core mechanisms; evaluating only the effect of tools but ignoring the optimal combination of governance tools, and paying attention only to the traditional pollutants and disregarding the latest air pollution. Accordingly, this paper finds that the research should be expanded from four aspects, which include taking into account the co-governance of new air pollution, clarifying the relationship between the various types of air pollutants and the driving factors, building a multi-disciplinary research framework for co-governance, and optimizing the combination of governance policies and technical tools in order to realize high-quality development of China.
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http://dx.doi.org/10.1007/s11356-021-13642-xDOI Listing
May 2021

Performance and efficiency of machine learning algorithms for analyzing rectangular biomedical data.

Lab Invest 2021 04 11;101(4):430-441. Epub 2021 Feb 11.

Department of Pathology, Princeton Medical Center, Plainsboro, NJ, USA.

Most biomedical datasets, including those of 'omics, population studies, and surveys, are rectangular in shape and have few missing data. Recently, their sample sizes have grown significantly. Rigorous analyses on these large datasets demand considerably more efficient and more accurate algorithms. Machine learning (ML) algorithms have been used to classify outcomes in biomedical datasets, including random forests (RF), decision tree (DT), artificial neural networks (ANN), and support vector machine (SVM). However, their performance and efficiency in classifying multi-category outcomes of rectangular data are poorly understood. Therefore, we compared these metrics among the 4 ML algorithms. As an example, we created a large rectangular dataset using the female breast cancers in the surveillance, epidemiology, and end results-18 database, which were diagnosed in 2004 and followed up until December 2016. The outcome was the five-category cause of death, namely alive, non-breast cancer, breast cancer, cardiovascular disease, and other cause. We analyzed the 54 dichotomized features from ~45,000 patients using MatLab (version 2018a) and the tenfold cross-validation approach. The accuracy in classifying five-category cause of death with DT, RF, ANN, and SVM was 69.21%, 70.23%, 70.16%, and 69.06%, respectively, which was higher than the accuracy of 68.12% with multinomial logistic regression. Based on the features' information entropy, we optimized dimension reduction (i.e., reduce the number of features in models). We found 32 or more features were required to maintain similar accuracy, while the running time decreased from 55.57 s for 54 features to 25.99 s for 32 features in RF, from 12.92 s to 10.48 s in ANN, and from 175.50 s to 67.81 s in SVM. In summary, we here show that RF, DT, ANN, and SVM had similar accuracy for classifying multi-category outcomes in this large rectangular dataset. Dimension reduction based on information gain will increase the model's efficiency while maintaining classification accuracy.
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http://dx.doi.org/10.1038/s41374-020-00525-xDOI Listing
April 2021

Roxadustat in treating anemia in dialysis patients (ROAD): protocol and rationale of a multicenter prospective observational cohort study.

BMC Nephrol 2021 01 13;22(1):28. Epub 2021 Jan 13.

Renal Department and Nephrology Institute, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West 2nd Duan, 1st Circle Road, Qingyang District, Chengdu, Sichuan, China.

Background: Roxadustat has been shown effective in treating patients with anemia due to chronic kidney disease. However, its long-term effect on clinical outcomes and socioeconomic burden and safety remains unclear.

Methods/design: This is a multicenter, prospective, longitudinal observational cohort study assessing if Roxadustat improves prognosis in dialysis patients. Primary outcomes will be major adverse cardiovascular events (MACE), defined as composites of cardiovascular death, myocardial infarction, cerebral infarction, hospitalization because of heart failure; all-cause mortality, and annual economic costs in two years. The data will be collected via Research electronic data capture (REDCap) based database as well as software-based dialysis registry of Sichuan province. The primary outcomes for the ROAD study participants will be compared with those in the dialysis registry cohort. Data at baseline and study follow up will also be compared to assess the association between Roxadustat and long-term clinical outcomes.

Discussion: The main objective of this study is to the assess long-term association of Roxadustat on MACE, all-cause mortality, socio-economic burden, safety in dialysis patients, which will provide guidance for designing further large randomized controlled trials to investigate this clinic question.

Study Registration: The study has been registered in Chinese Clinical Trials Registry (ROAD, ROxadustat in treating Anemia in Dialysis patients, registration number ChiCTR1900025765) and provincial observational cohort database (Renal disEAse observational CoHort database, REACH, ChiCTR1900024926), registered 07 September 2019, http://www.chictr.org.cn .
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http://dx.doi.org/10.1186/s12882-021-02229-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805134PMC
January 2021

A mouse allergic asthma model induced by shrimp tropomyosin.

Int Immunopharmacol 2021 Feb 25;91:107289. Epub 2020 Dec 25.

Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225009, China; Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou University Medical College, Yangzhou 225009, China; Xinghua People's Hospital, Yangzhou University, Xinghua, Jiangsu 225700, China. Electronic address:

Allergic asthma remains an important worldwide health issue. Animal models are valuable for understanding the pathophysiological mechanisms of asthma and the development of effective therapeutics. This study aims to develop an alternative murine model induced by shrimp tropomyosin (ST) instead of ovalbumin (OVA). To investigate responses to short-term exposure to antigens, mice were sensitized with intraperitoneal injections of ST or ST plus aluminum adjuvant on days 0, 7, 14 followed by an intranasal challenge with ST for seven consecutive days. We reveal that sensitization with ST alone or ST plus aluminum induces significant levels of serum total IgE and ST-specific IgE in mice. Challenge results show that ST causes severe eosinophilic airway inflammation. Histology analysis of the lung tissues demonstrates airway inflammation and mucus hypersecretion within the bronchi in mice exposed to ST. Analysis of the cell composition in bronchoalveolar lavage fluid (BALF) shows a significant increase in eosinophil count in ST alone and ST plus aluminum groups. We also detect increased CD4 T lymphocytes in lung tissues and production of helper T cell type 2-associated cytokines (IL-4 and IL-5) in BALF. In addition, airway hyperresponsiveness to methacholine in ST alone and ST plus aluminum groups is much higher than that in control groups. For the chronic model, mice were sensitized by ST or ST plus aluminum adjuvant for 3weeks and challenged with ST for 6weeks. We find severe structural changes in animals upon prolonged exposure to ST, including goblet cell hyperplasia, collagen deposition, and smooth muscle thickening. In conclusion, ST-induced asthma is a simple murine model for studying pathogenesis of asthma and evaluating new therapeutic drugs.
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http://dx.doi.org/10.1016/j.intimp.2020.107289DOI Listing
February 2021

miR-144/451 inhibits c-Myc to promote erythroid differentiation.

FASEB J 2020 10 16;34(10):13194-13210. Epub 2020 Aug 16.

Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China.

Ablation of miR-144/451 disrupts homeostasis of erythropoiesis. Myc, a protooncogenic protein, is essential for erythroblast proliferation but commits rapid downregulation during erythroid maturation. How erythroblasts orchestrate maturation processes through coding and non-coding genes is largely unknown. In this study, we use miR-144/451 knockout mice as in vivo model, G1E, MEL erythroblast lines and erythroblasts from fresh mouse fetal livers as in vitro systems to demonstrate that targeted depletion of miR-144/451 blocks erythroid nuclear condensation and enucleation. This is due, at least in part, to the continued high expression of Myc in erythroblasts when miR-144/451 is absent. Specifically, miR-144/451 directly inhibits Myc in erythroblasts. Loss of miR-144/451 locus derepresses, and thus, increases the expression of Myc. Sustained high levels of Myc in miR-144/451-depleted erythroblasts blocks erythroid differentiation. Moreover, Myc reversely regulates the expression of miR-144/451, forming a positive miR-144/451-Myc feedback to ensure the complete shutoff of Myc during erythropoiesis. Given that erythroid-specific transcription factor GATA1 activates miR-144/451 and inactivates Myc, our findings indicate that GATA1-miR-144/451-Myc network safeguards normal erythroid differentiation. Our findings also demonstrate that disruption of the miR-144/451-Myc crosstalk causes anemia, suggesting that miR-144/451 might be a potential therapeutic target in red cell diseases.
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http://dx.doi.org/10.1096/fj.202000941RDOI Listing
October 2020

State heterogeneity in the associations of human mobility with COVID-19 epidemics in the European Union.

Am J Transl Res 2020 15;12(11):7430-7438. Epub 2020 Nov 15.

Department of Biological Sciences, Rutgers University Newark NJ, USA.

Background: Human mobility was associated with epidemic changes of coronavirus disease 2019 (COVID-19) in the countries, where strict public health interventions reduced human mobility and COVID-19 epidemics. But its association with COVID-19 epidemics in the European Union (EU) is unclear.

Methods: In this quasi-experimental interrupted time-series study, we modelled trends in human mobility and epidemics of COVID-19 in 27 EU states between January 15 and May 9, 2020. The associations of lockdown-date, and turning points of these trends were assessed.

Results: There were 982,332 laboratory-confirmed COVID-19 cases in the EU states (median 7,896, interquartile 1,689 to 25,702 for individual states) during the study-period. COVID-19 and human mobility had 3 trend-segments, including an upward trend in COVID-19 daily incidence and a downward trend in most human mobilities in the middle segment. Compared with the states farther from Italy, the state-wide lockdown dates were more likely linked to turning points of human mobilities in the states closer to Italy, which were also more likely linked to second turning points of COVID-19 epidemics. Among the examined human mobilities, the second turning points in driving mobility and the first turning points in parks mobility were the best factors that connected lockdown dates and COVID-19 epidemics in the EU states closer to Italy.

Conclusions: We show state- and mobility-heterogeneity in the associations of public health interventions and human mobility with the changes of COVID-19 epidemics in the EU. These findings may help inform policymakers on the best timing and monitoring-parameters of state-level interventions in the EU.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724319PMC
November 2020

Targeting DNA to the endoplasmic reticulum efficiently enhances gene delivery and therapy.

Nanoscale 2020 Sep 28;12(35):18249-18262. Epub 2020 Aug 28.

College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P. R. China.

Gene therapy mediated by non-viral carriers is gaining an increasing popularity due to its high biosafety and the convenience of production on a large scale, yet inefficient gene delivery is a limiting obstacle. Few gene vectors can avoid the endosome-lysosome route, and as a result, their DNA payloads are easily decomposed during transfection. Herein, a peptide (pardaxin, PAR)-modified cationic liposome (PAR-Lipo) targeting the endoplasmic reticulum (ER) was developed for improving the gene delivery efficiency. Interestingly, compared to non-PAR-modified cationic liposomes (Non-Lipos) and Lipofectamine 2000 (Lipo 2000, a commercial genetic vector), PAR-Lipos showed remarkably higher gene delivery efficiency in vitro and better antitumor efficacy in vivo. It was demonstrated that PAR-Lipos could be accumulated into the ER via a non-lysosome intracellular route after cellular internalization, which induced the retention of the DNA payload in the ER close to the nucleus, while Non-Lipos, like most conventional cationic carriers, mainly presented lysosomal retention after their endocytosis. The unique intracellular transport behavior of PAR-Lipos can enhance the protection of the DNA payload, prolong their residence time in the cell, and promote their entry into the nucleus relying on the intimate relationship between the ER and nuclear membrane, which is the explanation for the enhanced gene-therapy effect mediated by PAR-Lipos. Our research may provide alternative means of efficiently delivering genes in cells.
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http://dx.doi.org/10.1039/d0nr03156aDOI Listing
September 2020

Impact of Environmental Pollution on Health-Evidence from Cities in China.

Soc Work Public Health 2020 07 13;35(6):413-430. Epub 2020 Aug 13.

College of Economics and Management, Shandong University of Science and Technology , Qingdao, China.

Doubtless, China's long-term extensive development model has exacerbated environmental pollution, thus posing a great threat to the health of its residents. Against this background, the present paper constructs a comprehensive system for evaluating environmental pollution from the perspective of environmental pollution and natural purification, and then empirically analyzes the impact of environmental pollution on the "near-term health," "self-rated health", and "mental health" of Chinese residents via the Hierarchical Linear Model based on the data from China Family Panel Studies in 2016. This paper focuses on the impact of environmental pollution on physical health as well as on mental health. The results are as follows: (1) although environmental pollution in China has no significant negative impact on the "near-term health" of residents, it can reduce the levels of "self-rated health" and "mental health" of residents; (2) environmental pollution causes more health losses to the low-income group and residents in underdeveloped cities in central and western China. It is argued that perfecting public services is an important way to improve residents' physical and mental health in the process of urbanization in China.
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http://dx.doi.org/10.1080/19371918.2020.1805084DOI Listing
July 2020

Nitrogen-doped carbon supported ZnO as highly stable heterogeneous catalysts for transesterification synthesis of ethyl methyl carbonate.

J Colloid Interface Sci 2021 Jan 21;581(Pt A):126-134. Epub 2020 Jul 21.

Key Laboratory of Surface and Interface Chemistry of Jilin Province, College of Chemistry, Jilin University, Changchun 130012, PR China. Electronic address:

Nitrogen-doped carbon material (NCM) supported ZnO catalysts were prepared by wet impregnation method, following a high-temperature thermal treatment process. The resultant ZnO/NCM catalysts calcined at different temperatures were characterized by X-ray diffraction (XRD), Raman spectroscopy, N adsorption-desorption, elemental analysis, X-ray photoelectron spectroscopy (XPS) to investigate their physicochemical properties and the interaction between ZnO and NCM support. Their catalytic properties were studied by liquid phase transesterification of dimethyl carbonate (DMC) with diethyl carbonate (DEC). Of these the catalyst calcined at 800 °C, named ZnO/NCM-800 exhibits the highest catalytic activity, as well as excellent stability and recyclability for the synthesis of ethyl methyl carbonate (EMC). The NCM support possesses abundant mesopores, rich surface oxygen-containing and nitrogen-containing functional groups, which are beneficial to build relatively strong interaction between ZnO nanoparticles and the NCM support, resulting in the generation of a highly active and stable acidic-basic bifunctional catalyst for the transesterification of DMC with DEC.
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http://dx.doi.org/10.1016/j.jcis.2020.07.095DOI Listing
January 2021

Appropriate Delivery of the CRISPR/Cas9 System through the Nonlysosomal Route: Application for Therapeutic Gene Editing.

Adv Sci (Weinh) 2020 Jul 13;7(14):1903381. Epub 2020 Jun 13.

College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 P. R. China.

The development of gene delivery has attracted increasing attention, especially when the introduction and application of the CRISPR/Cas9 gene editing system appears promising for gene therapy. However, ensuring biosafety and high gene editing efficiency at the same time poses a great challenge for its in vivo applications. Herein, a pardaxin peptide (PAR)-modified cationic liposome (PAR-Lipo) is developed. The results are indicative that significantly enhanced gene editing efficiency can be obtained through the mediation of PAR-Lipos compared to non-Lipos (non-PAR-modified liposomes) and Lipofectamine 2000, owing to its protection toward carried nucleotide by the prevention of lysosomal capture, prolongation of retention time in cells through the accumulation in the endoplasmic reticulum (ER), and more importantly, facilitation of the nuclear access via an ER-nucleus route. Accumulation of PAR-Lipos in the ER may improve the binding of Cas9 and sgRNA, thus further contributing to the eventually enhanced gene editing efficiency. Given their high biosafety, PAR-Lipos are used to mediate the knockout of the oncogene CDC6 in vivo, which results in significant tumor growth inhibition. This work may provide a useful reference for enhancing the delivery of gene editing systems, thus improving the potential for their future clinical applications.
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http://dx.doi.org/10.1002/advs.201903381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375254PMC
July 2020

A novel LncRNA transcript, RBAT1, accelerates tumorigenesis through interacting with HNRNPL and cis-activating E2F3.

Mol Cancer 2020 07 15;19(1):115. Epub 2020 Jul 15.

Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.

Background: Long non-coding RNAs (lncRNAs) have been identified as important epigenetic regulators that play critical roles in human cancers. However, the regulatory functions of lncRNAs in tumorigenesis remains to be elucidated. Here, we aimed to investigate the molecular mechanisms and potential clinical application of a novel lncRNA, retinoblastoma associated transcript-1 (RBAT1), in tumorigenesis.

Methods: RBAT1 expression was determined by real-time PCR in both retinoblastoma (Rb) and bladder cancer (BCa) cell lines and clinical tissues. Chromatin isolation using RNA purification (ChIRP) assays were performed to identify RBAT1-interacting proteins. Patient-derived xenograft (PDX) retinoblastoma models were established to test the therapeutic potential of RBAT1-targeting GapmeRs.

Results: Here, we found that RBAT1 expression was significantly higher in Rb and BCa tissues than that in adjacent tissues. Functional assays revealed that RBAT1 accelerated tumorigenesis both in vitro and in vivo. Mechanistically, RBAT1 recruited HNRNPL protein to E2F3 promoter, thereby activating E2F3 transcription. Therapeutically, GapmeR-mediated RBAT1 silencing significantly inhibited tumorigenesis in orthotopic xenograft retinoblastoma models derived from Rb cell lines and Rb primary cells.

Conclusions: RBAT1 overexpression upregulates a known oncogene, E2F3, via directly recruiting HNPNPL to its promoter and cis-activating its expression. Our finding provides a novel mechanism of lncRNA biology and provides potential targets for diagnosis and treatment of Rb and BCa.
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http://dx.doi.org/10.1186/s12943-020-01232-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362570PMC
July 2020

Trends and prediction in daily incidence and deaths of COVID-19 in the United States: a search-interest based model.

medRxiv 2020 Apr 20. Epub 2020 Apr 20.

Background And Objectives: The coronavirus disease 2019 (COVID-19) infected 586,000 patients in the U.S. However, the COVDI-19 daily incidence and deaths in the U.S. are poorly understood. Internet search interest was found highly correlated with COVID-19 daily incidence in China, but not yet applied to the U.S. Therefore, we examined the association of search interest with COVID-19 daily incidence and deaths in the U.S.

Methods: We extracted the COVDI-19 daily incidence and death data in the U.S. from two population-based datasets. The search interest of COVID-19 related terms was obtained using Google Trends. Pearson correlation test and general linear model were used to examine correlations and predict future trends, respectively.

Results: There were 555,245 new cases and 22,019 deaths of COVID-19 reported in the U.S. from March 1 to April 12, 2020. The search interest of COVID, COVID pneumonia, and COVID heart were correlated with COVDI-19 daily incidence with about 12-day of delay (Pearson r=0.978, 0.978 and 0.979, respectively) and deaths with 19-day of delay (Pearson r=0.963, 0.958 and 0.970, respectively). The COVID-19 daily incidence and deaths appeared to both peak on April 10. The 4-day follow-up with prospectively collected data showed moderate to good accuracies for predicting new cases (Pearson r=-0.641 to -0.833) and poor to good acuracies for daily new deaths (Pearson r=0.365 to 0.935).

Conclusions: Search terms related to COVID-19 are highly correlated with the trends in COVID-19 daily incidence and deaths in the U.S. The prediction-models based on the search interest trend reached moderate to good accuracies.
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http://dx.doi.org/10.1101/2020.04.15.20064485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276031PMC
April 2020

Ultrafine Ru species within confined space: An efficient adsorbent for ultra-deep desulfurization of benzene.

Chemosphere 2020 Oct 14;256:127077. Epub 2020 May 14.

College of Chemistry and Chemical Engineering, Dezhou University, Dezhou, 253013, China. Electronic address:

The ultra-deep adsorptive desulfurization (ppb level) of benzene remains a challenging subject with the need to construct efficient adsorbent systems. Herein, a kind of ruthenium-based adsorbent functionalized with bimetallic Ru-Al was rationally designed using AlO as support (denoted as 0.8%Ru-1.2%Al/AlO). It was found that the co-anchoring of Ru and Al species endows the Ru-based adsorbent unique adsorption capability, which is able to completely eliminate sulfur compounds in benzene, and exhibiting a much higher breakthrough sulfur capacity than that of the 0.8%Ru/AlO. Remarkably, under the industrial experiment conditions, 0.8%Ru-1.2%Al/AlO exhibited excellent long-term stability for more than 1200 h, showing the potential for industrial application. Various characterization techniques, including BET, XRD, SEM, TEM, TPD-MS, TPR and XPS, were used to investigate the correlation between the adsorption performance and the microstructure of the adsorbents. Over 0.8%Ru-1.2%Al/AlO, the ultra-thin aluminum additive is beneficial to improve the dispersion of Ru species, which therefore exhibits desirable desulfurization efficiency. Moreover, the enhanced performance is also correlated to the presence of the suitable Ru active centers generated from the selective coverage by Al species. It leads to an optimal exposure of the Ru active centers, which would facilitate the interaction of S-Ru and the improvement of the desulfurization activity.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127077DOI Listing
October 2020

Trends and prediction in daily incidence of novel coronavirus infection in China, Hubei Province and Wuhan City: an application of Farr's law.

Am J Transl Res 2020 15;12(4):1355-1361. Epub 2020 Apr 15.

Department of Pathology, Princeton Medical Center Plainsboro, NJ, USA.

Background: The recent outbreak of novel coronavirus (2019-nCoV) has infected tens of thousands of patients in China. Studies have forecasted future trends of the incidence of 2019-nCoV infection, but appeared unsuccessful. Farr's law is a classic epidemiology theory/practice for predicting epidemics. Therefore, we used and validated a model based on Farr's law to predict the daily-incidence of 2019-nCoV infection in China and 2 regions of high-incidence.

Methods: We extracted the 2019-nCoV incidence data of China, Hubei Province and Wuhan City from websites of the Chinese and Hubei health commissions. A model based on Farr's law was developed using the data available on Feb. 8, 2020, and used to predict daily-incidence of 2019-nCoV infection in China, Hubei Province and Wuhan City afterward.

Results: We observed 50,995 (37,001 on or before Feb. 8) incident cases in China from January 16 to February 15, 2020. The daily-incidence has peaked in China, Hubei Providence and Wuhan City, but with different downward slopes. If no major changes occur, our model shows that the daily-incidence of 2019-nCoV will drop to single-digit by February 25 for China and Hubei Province, but by March 8 for Wuhan city. However, predicted 75% confidence intervals of daily-incidence in all 3 regions of interest had an upward trend. The predicted trends overall match the prospectively-collected data, confirming usefulness of these models.

Conclusions: This study shows the daily-incidence of 2019-nCoV in China, Hubei Province and Wuhan City has reached the peak and was decreasing. However, there is a possibility of upward trend.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191162PMC
April 2020

Trends and Prediction in Daily New Cases and Deaths of COVID-19 in the United States: An Internet Search-Interest Based Model.

Explor Res Hypothesis Med 2020 Apr 18;5(2):1-6. Epub 2020 Apr 18.

Department of Biological Sciences, Rutgers University Newark, NJ, USA.

Background And Objectives: The daily incidence and deaths of coronavirus disease 2019 (COVID-19) in the USA are poorly understood. Internet search interest was found to be correlated with COVID-19 daily incidence in China, but has not yet been applied to the USA. Therefore, we examined the association of internet search-interest with COVID-19 daily incidence and deaths in the USA.

Methods: We extracted COVID-19 daily new cases and deaths in the USA from two population-based datasets, namely 1-point-3-acres.com and the Johns Hopkins COVID-19 data repository. The internet search-interest of COVID-19-related terms was obtained using Google Trends. The Pearson correlation test and general linear model were used to examine correlations and predict trends, respectively.

Results: There were 636,282 new cases and,325 deaths of COVID-19 in the USA from March 1 to April 15, 2020, with a crude mortality of 4.45%. The daily new cases peaked at 35,098 cases on April 10, 2020 and the daily deaths peaked at 2,494 on April 15, 2020. The search interest of COVID, "COVID pneumonia" and "COVID heart" were correlated with COVID-19 daily incidence, with 12 or 14 days of delay (Pearson's = 0.978, 0.978 and 0.979, respectively) and deaths with 19 days of delay (Pearson's = 0.963, 0.958 and 0.970, respectively). The 7-day follow-up with prospectively collected data showed no significant correlations of the observed data with the predicted daily new cases or daily deaths, using search interest of COVID, COVID heart, and COVID pneumonia.

Conclusions: Search terms related to COVID-19 are highly correlated with the COVID-19 daily new cases and deaths in the USA.
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http://dx.doi.org/10.14218/ERHM.2020.00023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176069PMC
April 2020

A new simple score of chronic cough: cough evaluation test.

BMC Pulm Med 2020 Mar 20;20(1):68. Epub 2020 Mar 20.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Rd, Guangzhou, Guangdong, 510120, P. R. China.

Background: Chronic cough has an important impact on physical, social and psychological aspects. A simple and effective method to assess different aspects of chronic cough severity is required. We aimed to develop a simple, self-completed test, Cough Evaluation Test (CET), to evaluate cough severity and its impact on health.

Method: The items of preliminary CET were generated based on literature review and clinical practice. Items reduction was conducted by modified Delphi method. Patients with chronic cough were recruited to complete CET, Cough Visual Analog Scales (VAS), Mandarin Chinese version of the Leicester Cough Questionnaire (LCQ-MC), and Cough Symptom Score (CSS). Reassessments were performed at 1 week apart before treatment, and after more than 2 weeks treatments. Concurrent validation, internal consistency, repeatability, responsiveness and the minimal important difference (MID) were determined.

Results: CET consists of five items with a 5-point Likert scale (1-5 scaling of items, 5-25 score range). The Cronbach's alpha values for CET was 0.80. CET showed a stronger correlation with LCQ-MC (r = - 0.74) compared to that between LCQ-MC with VAS (r = - 0.61). CET also showed a stronger correlation with VAS (r = 0.70) compared to that between VAS with other measures. Intraclass correlation coefficients for CET was 0.84. In patients undergoing treatment, CET scores significantly changed (p < 0.0001). The MID of CET was 2.

Conclusion: Cough Evaluate Test is a reliable, valid and responsive tool to simply evaluate impact of cough on physical, social and psychological aspects.
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http://dx.doi.org/10.1186/s12890-020-1106-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083055PMC
March 2020

Virus-like Nonvirus Cationic Liposome for Efficient Gene Delivery via Endoplasmic Reticulum Pathway.

ACS Cent Sci 2020 Feb 11;6(2):174-188. Epub 2020 Feb 11.

College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P. R. China.

Gene vectors play a critical role in gene therapy. To achieve efficient transfection, we developed a novel nonvirus cationic liposome (Lipo-Par), which was bound covalently with the cationic polypeptide pardaxin (Par). Interestingly, the Lipo-Pars exhibited highly enhanced gene transfection efficiency in various cell lines compared to that of the non-Par-bonded liposomes (Lipo-Nons). As a result, the internalization and intracellular transport mechanisms of the Lipo-Pars were investigated, and the findings indicated their ability to actively target the endoplasmic reticulum (ER) by moving along the cell cytoskeleton after undergoing caveolin-mediated endocytosis. This intracellular transport process is similar to that of some viruses. It was also found that ER stress and calcium level disturbances can affect the Lipo-Par-mediated expression of certain exogenous genes. A possible, yet non-negligible explanation for the high transfection efficiency of the Lipo-Par is its virus-like intracellular behavior and the intimate relationship between the ER membrane and the nuclear envelope.
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http://dx.doi.org/10.1021/acscentsci.9b01052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047280PMC
February 2020

A cabazitaxel liposome for increased solubility, enhanced antitumor effect and reduced systemic toxicity.

Asian J Pharm Sci 2019 Nov 20;14(6):658-667. Epub 2018 Nov 20.

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

The potential side effects of cabazitaxel (CBZ) in the field of cancer treatment have become a great limitation to its further clinical application. Liposomal delivery is a well-established approach to increase the therapeutic index of hydrophobic drugs. In this study, a PEG-modified liposome was developed for efficiently encapsulating CBZ, thus enhancing its specific tumor inhibition effect and reducing the systemic toxicity. It was found that the loading efficiency of CBZ into the liposome could be improved with the increase of lipophilic materials, as it could be over 80% under the weight ratio of 20:1 (total lipid: CBZ). The diameter of CBZ loaded liposome ([email protected]) was ∼100 nm. And the liposome suspending in aqueous medium was stable at 4 °C for at least one month, according to the change of its size distribution. The killing ability of [email protected] to cancer cells was significantly lower comparing to that of CBZ solution, which could be attributed to the slow release of CBZ from the liposomes. However, [email protected] could induce an obvious apoptosis of the cancer cells at low concentration. Furthermore, [email protected] exhibited an expressively enhanced tumor growth inhibition effect comparing to CBZ solution. More importantly, [email protected] showed an obviously higher biosafety proved by lower hemolysis probability, stable body weight of mice during the whole experiment and no obvious lesion in histology analysis. Our work provided a useful reference of the formulation of CBZ, which had potential for greater clinical application.
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http://dx.doi.org/10.1016/j.ajps.2018.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7032206PMC
November 2019

Different MicroRNA Families Involved in Regulating High Temperature Stress Response during Cotton ( L.) Anther Development.

Int J Mol Sci 2020 Feb 14;21(4). Epub 2020 Feb 14.

College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China.

MicroRNAs (miRNAs) are small molecule RNAs widely involved in responses to plant abiotic stresses. We performed small RNA sequencing of cotton anthers at four developmental stages under normal and high temperature (NT and HT, respectively) conditions to investigate the stress response characteristics of miRNA to HT. A total of 77 miRNAs, including 33 known miRNAs and 44 novel miRNAs, were identified, and 41 and 28 miRNAs were differentially expressed under NT and HT stress conditions, respectively. The sporogenous cell proliferation (SCP), meiotic phase (MP), microspore release period (MRP), and pollen maturity (PM) stages had 10 (including 12 miRNAs), four (including six miRNAs), four (including five miRNAs), and seven (including 11 miRNAs) HT stress-responsive miRNA families, respectively, which were identified after removing the changes in genotype-specific miRNAs under NT condition. Seven miRNA families (miR2949, miR167, and miR160 at the SCP stage; miR156 and miR172 at the MP stage; miR156 at the MRP stage; and miR393 and miR3476 at the PM stage), which had expression abundance of more than 10% of the total expression abundance, served as the main regulators responding to HT stress with positive or negative regulation patterns. These miRNAs orchestrated the expression of the corresponding target genes and led to different responses in the HT-tolerant and the HT-sensitive lines. The results revealed that the HT stress response of miRNAs in cotton anthers were stage-specific and differed with the development of anthers. Our study may enhance the understanding of the response of miRNAs to HT stress in cotton anthers and may clarify the mechanism of plant tolerance to HT stress.
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http://dx.doi.org/10.3390/ijms21041280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072957PMC
February 2020

Patterns of sexual health in patients with breast cancer in China: a latent class analysis.

Support Care Cancer 2020 Nov 14;28(11):5147-5156. Epub 2020 Feb 14.

School of Nursing, Fudan University, Shanghai, China.

Purpose: This study aimed to identify unobserved distinct latent classes/subgroups of breast cancer (BC) patients in China with respect to various sexual health measures and examine the association of the latent membership with individual characteristics.

Methods: In a cross-sectional study, 123 BC patients were analyzed. Their sexual health was measured using the Female Sexual Functioning Index (FSFI). Latent class analysis (LCA) was used to examine the patterns of sexual health in patients. Associations of the latent class membership with individual characteristics were examined using multinomial logistic regression.

Results: Three a priori unknown distinct latent classes of patients were identified with respect to the 19 FSFI sexual health measures: 50 patients (41.6%) were classified in class 1 "No Impairment Group," 49 patients (39.4%) in class 2 "Organic Sexual Dysfunction Group," and 24 patients (19.1%) in class 3 "Poor Sexual Health Group." Income and anxiety were positively, whereas disease duration was negatively associated with the likelihood of being in class 2 than in class 1, patients with recurrence of cancer were likely to be in classes 2 and 3. Patients classified in class 3 were more likely to have better prior body image and have more severe menopausal symptoms, whereas less likely to have better post body image and have better partner relationships.

Conclusion: The findings revealed the heterogeneity of sexual health among BC patients in China and may guide to identify the high-risk patients and enable early intervention.
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http://dx.doi.org/10.1007/s00520-020-05332-0DOI Listing
November 2020

Anti-leucine-rich Glioma Inactivated-1 Encephalitis Associated with Essential Thrombocythemia.

Intern Med 2020 15;59(2):271-275. Epub 2020 Jan 15.

Department of Neurology, Liaocheng People's Hospital; Liaocheng Clinical School, Taishan Medical University, PR China.

Anti-leucine-rich glioma inactivated-1 (anti-LGI1) encephalitis is a subgroup of autoimmune encephalitis. We herein report the case of a 60-year-old man who presented with typical symptoms, including short-term memory loss, mental abnormalities, hyponatremia and seizures characterized by faciobrachial dystonic seizures and who was diagnosed with anti-LGI1 encephalitis. At the same time, he was diagnosed with essential thrombocythemia. A significant improvement was obtained by treatment with corticosteroid, immunoglobulin, mycophenolate mofetil, and hydroxyurea. Autoimmune diseases are associated with a significantly increased risk of developing myeloproliferative neoplasms, which may explain the coexistence of anti-LGI1 encephalitis and essential thrombocythema in this patient; however, but more cases and studies are needed to determine whether there is any correlation between these conditions.
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http://dx.doi.org/10.2169/internalmedicine.2963-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008042PMC
April 2020

HLA-DQB1 and HLA-DRB1 Variants Confer Susceptibility to Latent Autoimmune Diabetes in Adults: Relative Predispositional Effects among Allele Groups.

Genes (Basel) 2019 09 13;10(9). Epub 2019 Sep 13.

Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan Scientific Research Center, Guangdong Medical University, Dongguan, Guangdong 523808, China.

Latent autoimmune diabetes in adults (LADA) was recently demonstrated to be the most frequent form of adult-onset autoimmune diabetes mellitus. Case-control studies have investigated the relationship between human leukocyte antigen (HLA)-DQB1 and HLA-DRB1 polymorphisms and LADA risk, but their conclusions are inconsistent. This study aimed to more precisely explore the correlation between these HLA gene variants and LADA development. Eight databases, including PubMed, Embase, and Medline, were systematically searched for relevant studies up to September 15, 2018. We performed this retrospective study using meta-analysis and relative predispositional effect (RPE) methods. The meta-analysis results indicated that DQB1*02 (odds ratio (OR) = 1.685, < 0.005) and DQB1*06 (OR = 0.604, = 0.010) have opposite effects on susceptibility to LADA, while a significant decrease in LADA risk caused by DQB1*05 (OR = 0.764, = 0.100) disappeared upon Bonferroni correction. The RPE method confirmed the roles of DQB1*02 (χ² = 46.475, < 0.001) and DQB1*06 (χ² = 17.883, < 0.001) and further suggested protective effects of DQB1*05 (χ² = 16.496, < 0.001). Additionally, the meta-analysis results showed that DRB1*03 (OR = 2.685, < 0.013), DRB1*04 (OR = 1.954, < 0.013), and DRB1*09 (OR = 1.346, < 0.013) are associated with increased LADA risk, while DRB1*12 (OR = 0.600, < 0.013) and DRB1*13 (OR = 0.583, < 0.013) carriers have a decreased risk of developing LADA. Furthermore, the RPE method revealed that DRB1*03 (χ² = 98.754, < 0.001), DRB1*04 (χ² = 94.685, < 0.001), DRB1*09 (χ² = 40.489, < 0.001), DRB1*01 (χ² = 12.181, < 0.001), DRB1*07 (χ² = 10.882, = 0.001), and DRB1*08 (χ² = 5.000, = 0.025) play protective roles against LADA. LADA showed a close relationship with genetic polymorphisms of HLA-DQB1 and WHLA-DRB1, which could contribute to a better understanding of disease pathogenesis and the identification of predisposing loci in the diagnosis and treatment of LADA.
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http://dx.doi.org/10.3390/genes10090710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771152PMC
September 2019

Translation, Validity, and Reliability of the Chinese Version of the Breast Cancer Survivor Self-efficacy Scale in China.

Cancer Nurs 2019 Sep/Oct;42(5):E31-E40

Author Affiliations: School of Nursing, Second Military Medical University, Shanghai (Mss Yuan and Wu and Dr Yuan); and School of Nursing, Fudan University (Dr Yuan), China; and Ontario Cancer Institute and Faculty of Nursing, University of Toronto, Canada (Dr Howell).

Background: Self-efficacy is a crucial variable that is related to quality of life. Patients who have high self-efficacy will exert sufficient effort and have better health outcomes and improved quality of life. Appropriate and precise measurement of self-efficacy can help promote better care. The Breast Cancer Survivor Self-efficacy Scale (BCSES) is designed to measure the perceived confidence of breast cancer patients in managing the tasks for self-management. Originally developed in America, it has not been used in China.

Objectives: The aims of this study were to translate BCSES into Chinese and assess its psychometric properties among Chinese patients.

Methods: In phase 1, the translation of BCSES closely followed the Principles of Good Practices. In phase 2, data on reliability and validity were evaluated in terms of internal consistency, item-total correlations, test-retest reliability, criterion validity, and construct validity. A total sample of 630 native Chinese-speaking patients from 5 hospitals in China participated, including a pilot sample of 182 and a validation sample of 448.

Results: Minor modifications in 5 items were recommended after translation. Both exploratory and confirmatory factor analyses suggested a 2-factor structure was more ideal than the original 1-factor model. Cronbach's α coefficient for the Chinese version of BCSES was .82, intraclass correlation coefficient was 0.97, and item-total correlations were from 0.61 to 0.76.

Conclusions: The Chinese version of BCSES appears to be culturally appropriate, reliable, and valid for assessing self-efficacy among patients with breast cancer in China.

Implication For Practice: The Chinese version of BCSES could help measure the breast cancer patients' self-efficacy and provide evidence to develop culturally sensitive interventions for Chinese patients.
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http://dx.doi.org/10.1097/NCC.0000000000000637DOI Listing
April 2020

Effects of orthostatic hypotension on cognition in type 2 diabetes mellitus.

Ann Neurol 2019 11 27;86(5):754-761. Epub 2019 Aug 27.

Department of Neurology, Weihai Municipal Hospital and Weihai Clinical School of Shandong University, Weihai.

Objective: To evaluate the effect of a decrease in blood pressure (BP) fulfilling the diagnostic criteria for orthostatic hypotension (OH) on performance in each domain of cognitive function in patients with type 2 diabetes mellitus using a cross-sectional and within-group design.

Methods: Subjects were individuals without dementia and with type 2 diabetes mellitus, including 107 individuals without OH and 94 with OH (DMOH); 95 control participants were also included. BP was assessed in both the supine and standing positions. A detailed neuropsychological assessment was made in each posture for all subjects.

Results: There were statistically significant differences between the patients without OH and the DMOH group with regard to some cognitive measures while supine. Standing posture exacerbated and broadened cognitive deficits in the DMOH group for all measures in the different domains of cognition including executive functioning, memory, visuospatial skills, information processing speed, and attention. When group-specific supine scores were used as baseline anchors, both the patients without OH and the DMOH group showed cognitive changes when transitioning from a supine to a standing, upright position, with the DMOH group exhibiting a wider range of neuropsychological deficits in memory, visuospatial skills, executive function, and sustained attention, as well as significant changes in information processing speed.

Interpretation: These data demonstrate that type 2 diabetes mellitus patients with OH had transient, posture-mediated cognitive deficits in excess of those found in diabetes mellitus without OH. Understanding the effects of OH on cognition due to autonomic failure is important, particularly as clinical assessments and neuroimaging collect data only in the seated or supine positions. ANN NEUROL 2019;86:754-761.
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http://dx.doi.org/10.1002/ana.25578DOI Listing
November 2019

Targeting photodynamic and photothermal therapy to the endoplasmic reticulum enhances immunogenic cancer cell death.

Nat Commun 2019 07 26;10(1):3349. Epub 2019 Jul 26.

College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, 310058, Hangzhou, Zhejiang, P. R. China.

Immunogenic cell death (ICD)-associated immunogenicity can be evoked through reactive oxygen species (ROS) produced via endoplasmic reticulum (ER) stress. In this study, we generate a double ER-targeting strategy to realize photodynamic therapy (PDT) photothermal therapy (PTT) immunotherapy. This nanosystem consists of ER-targeting pardaxin (FAL) peptides modified-, indocyanine green (ICG) conjugated- hollow gold nanospheres (FAL-ICG-HAuNS), together with an oxygen-delivering hemoglobin (Hb) liposome (FAL-Hb lipo), designed to reverse hypoxia. Compared with non-targeting nanosystems, the ER-targeting naosystem induces robust ER stress and calreticulin (CRT) exposure on the cell surface under near-infrared (NIR) light irradiation. CRT, a marker for ICD, acts as an 'eat me' signal to stimulate the antigen presenting function of dendritic cells. As a result, a series of immunological responses are activated, including CD8 T cell proliferation and cytotoxic cytokine secretion. In conclusion, ER-targeting PDT-PTT promoted ICD-associated immunotherapy through direct ROS-based ER stress and exhibited enhanced anti-tumour efficacy.
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http://dx.doi.org/10.1038/s41467-019-11269-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659660PMC
July 2019
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