Publications by authors named "Miao Yu"

1,309 Publications

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High output achieved by sliding electrification of an electrospun nano-grating.

Nanoscale 2021 Oct 14. Epub 2021 Oct 14.

Collaborative Innovation Center for Nanomaterials & Devices, College of Physics, Qingdao University, Qingdao 266071, China.

The rapid development of flexible and wearable electronics has proposed a trend towards miniaturization, mobility, versatility and artificial intelligence. Triboelectric nanogenerators (TENGs) can make use of micro/nano multi-functional materials to harvest and store energy from the surrounding environment efficiently, which can drive smart portable electronics operating continuously and steadily. The increase in the output power density of the triboelectric nanogenerator requires new designs. In this work, a new grating TENG was proposed, and the two friction layers were fabricated by near-field electrospinning and conventional electrospinning with two parallel electrodes as a collector, respectively. The basic model of the simulation was simplified according to the highly ordered structure and the repeatability of the TENG grating structure. The effect of the effective contact area on the output of the TENG was further proved by fitting the calculation regularity of the two models with the experimental results. At the same time, the effect of the redundant electrode on the output of the TENG was verified by experiments. We found that this nanogenerator can achieve a very high output of 1800 W m due to a more refined grating structure combined with modification of the contact area. The TENG can also be used as a selfpowered sensor to detect mechanical signals, which requires no additional power source to drive it. Meanwhile, the anisotropic nature of the TENG can also be utilized to sense angles, lock devices or encrypt information. This output control technology provides a more effective idea for future output power improvement, that is, a new generation of high-output TENGs can be designed by effectively adjusting the corresponding contact area and electrode area.
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http://dx.doi.org/10.1039/d1nr04769hDOI Listing
October 2021

Raman Spectroscopic Characterization of Polymerization Kinetics of Cyanoacrylate Embolic Glues for Vascular Embolization.

Polymers (Basel) 2021 Sep 30;13(19). Epub 2021 Sep 30.

School of Optoelectronic Engineering and Instrumentation Science, Dalian University of Technology, Dalian 116024, China.

Endovascular glue embolization is a minimally invasive technique used to selectively reduce or block the blood supply to specific targeted vessels. Cyanoacrylate glues, mixed with radiopaque iodized oil, have been widely used for vascular embolization owing to their rapid polymerization rate, good penetration ability and low tissue toxicity. Nevertheless, in clinical practice, the selection of the glue-oil proportion and the manual injection process of mixtures are mostly based on empirical knowledge of operators, as the crucial physicochemical effect of polymerization kinetics has rarely been quantitatively investigated. In this study, the Raman spectroscopy is used for studying the polymerization kinetics of n-butyl-cyanoacrylate-based glues mixed with an iodized oil. To simulate the polymerization process during embolization, glue-oil mixtures upon contact with a protein ionic solution mimicking blood plasma are manually constructed and their polymerization kinetics are systematically characterized by Raman spectroscopy. The results demonstrate the feasibility of Raman spectroscopy in the characterization of polymerization kinetics of cyanoacrylate-based embolic glues. The polymerization process of cyanoacrylate-based mixtures consists of a fast polymerization phase followed by a slow phase. The propagation velocity and polymerization time primarily depend on the glue concentrations. The commonly used 50% mixture polymerizes 1 mm over ∼21.8 s, while it takes ∼51 min to extend to 5 mm. The results provide essential information for interventional radiologists to help them understand the polymerization kinetics of embolic glues and thus regulate the polymerization rate for effective embolization.
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http://dx.doi.org/10.3390/polym13193362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512224PMC
September 2021

Simultaneous imaging of hypochlorous acid and nitric oxide in live cells based on a dual-channel fluorescent probe.

Anal Chim Acta 2021 Oct 21;1183:338980. Epub 2021 Aug 21.

Research Centre of Chemical Biology, Yanbian University, Yanji 133002, China. Electronic address:

Both reactive oxygen species (ROS) and reactive nitrogen species (RNS) are inevitably produced during normal human metabolism. Various ROS and RNS together form tangled networks that play important roles in many physiological and pathological processes. Here we used 1,8-naphthalene diamine as a reactive group to develop a fluorescent probe, N-[2-(6-phenylethynyl)quinolinylmethyl]-1,8-diamino naphthalene (QBN), for HOCl and NO. QBN showed a "turn-on" fluorescent response at 464 nm to HOCl in the range of 0-75 μM with rapid responding time (10 s) and detection limit (0.11 ± 0.03 μM). Furthermore, a "turn-on" fluorescent responses at 512 nm to NO in the range of 0-40 μM with responding time (20 s) and detection limit (25.7 ± 3.4 nM) was found. The response mechanisms of QBN to HOCl and NO were discussed based on mass analysis of the different products. The dual-channel probe was then successfully applied for simultaneous imaging of both exogenous and endogenous HOCl and NO in live cells.
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http://dx.doi.org/10.1016/j.aca.2021.338980DOI Listing
October 2021

A Novel Medical Image Denoising Method Based on Conditional Generative Adversarial Network.

Comput Math Methods Med 2021 28;2021:9974017. Epub 2021 Sep 28.

School of Computer Science and Technology, Changchun University of Science and Technology, Changchun 130022, China.

Medical image quality is highly relative to clinical diagnosis and treatment, leading to a popular research topic of medical image denoising. Image denoising based on deep learning methods has attracted considerable attention owing to its excellent ability of automatic feature extraction. Most existing methods for medical image denoising adapted to certain types of noise have difficulties in handling spatially varying noise; meanwhile, image detail losses and structure changes occurred in the denoised image. Considering image context perception and structure preserving, this paper firstly introduces a medical image denoising method based on conditional generative adversarial network (CGAN) for various unknown noises. In the proposed architecture, noise image with the corresponding gradient image is merged as network conditional information, which enhances the contrast between the original signal and noise according to the structural specificity. A novel generator with residual dense blocks makes full use of the relationship among convolutional layers to explore image context. Furthermore, the reconstruction loss and WGAN loss are combined as the objective loss function to ensure the consistency of denoised image and real image. A series of experiments for medical image denoising are conducted with the denoising results of PSNR = 33.2642 and SSIM = 0.9206 on JSRT datasets and PSNR = 35.1086 and SSIM = 0.9328 on LIDC datasets. Compared with the state-of-the-art methods, the superior performance of the proposed method is outstanding.
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http://dx.doi.org/10.1155/2021/9974017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492295PMC
September 2021

LncRNA LINC00662 Exerts an Oncogenic Effect on Osteosarcoma by the miR-16-5p/ITPR1 Axis.

J Oncol 2021 28;2021:8493431. Epub 2021 Sep 28.

Department of Spine Surgery, Foshan Hospital of Traditional Chinese Medicine, Foshan 528000, Guangdong, China.

Background: Osteosarcoma (OS) is one of the most malignant bone tumors and has a high metastatic rate. Increasing research has demonstrated the vital roles of long noncoding RNAs (lncRNAs) in human cancers, including OS. LncRNA LINC00662 has been revealed to act as an oncogene involved in multiple tumor progression. This study aimed to investigate the expression pattern, function, and regulatory mechanism of LINC00662 in OS.

Methods: Patients who underwent OS surgery were involved in this study. Experiments including RT-qPCR, MTT, western blot, FISH, RNA pull-down, luciferase reporter, colony formation, transwell invasion and migration, and sphere formation assay were performed to investigate the regulatory role of LINC00662 in OS.

Results: In the present study, our findings demonstrated the upregulation of LINC00662 expression in OS tissues and cells, and high expression of LINC00662 predicted a poor clinical prognosis of patients' iNOS. Through a series of assays, LINC00662 knockdown suppressed OS cell proliferation, invasion, migration, and stemness property maintenance. Further mechanistical investigations indicated that LINC00662 functioned as a competing endogenous RNA (ceRNA) for sponging microRNA-16-5p (miR-16-5p) to upregulate the expression of IP receptor type 1 (ITPR1) in OS cells. Restoration assays validated the involvement of ITPR1 in LINC00662-mediated regulation of cell functions in OS.

Conclusion: LINC00662 exerts oncogenic functions in OS by targeting the miR-16-5p/ITPR1 axis.
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http://dx.doi.org/10.1155/2021/8493431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492273PMC
September 2021

Urinary and seminal plasma concentrations of phthalate metabolites in relation to spermatogenesis-related miRNA106a among men from an infertility clinic.

Chemosphere 2021 Oct 4;288(Pt 1):132464. Epub 2021 Oct 4.

Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. Electronic address:

Studies indicate that phthalates can disrupt spermatogenesis and lead to the reduction of semen quality. However, the underlying mechanisms remain unclear. This study aimed to examine the associations of phthalate exposures as individual chemicals and mixtures with spermatogenesis-related miRNA106a. We detected eight phthalate metabolites in repeated urine samples and a single seminal plasma specimen among 111 men from an infertility clinic in Wuhan, China. Spermatogenesis-related miRNA106a was measured in seminal plasma. We used multivariable linear regression and Bayesian kernel machine regression (BKMR) models to separately evaluate the associations of phthalate metabolites as individual chemicals and mixtures with spermatogenesis-related miRNA106a. Elevated tertiles of urinary mono (2-ethylhexyl) phthalate (MEHP) was associated with decreased miRNA106a (-61.71%; 95%CI: 81.92, -18.93% for the highest vs. lowest tertile; P for trend = 0.01). Similarly, an inverse exposure-response relationship between seminal plasma MEHP concentrations and miRNA106a was also observed (-59.44%; 95%CI: 79.19, -20.95% for the highest vs. lowest tertile; P for trend = 0.01). The BKMR models showed that the mixtures of seminal plasma phthalate metabolites were associated with decreased miRNA106a when the chemical mixtures were ≥35th percentile compared to their medians. Nonlinear associations with miRNA106a were estimated for urinary and seminal plasma MEHP while fixing other phthalate metabolites at their medians. Our findings suggest that mixtures of phthalate metabolites in seminal plasma were negatively associated with spermatogenesis-related miRNA106a, and individual MEHP was the major contributor to the adverse effects.
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http://dx.doi.org/10.1016/j.chemosphere.2021.132464DOI Listing
October 2021

Generation of Human Induced Pluripotent Stem Cells from Renal Epithelial Cells.

Methods Mol Biol 2021 Oct 6. Epub 2021 Oct 6.

Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou, China.

In the past decades, human induced pluripotent stem cells (iPSCs) have been generated by the ectopic expression of "Yamanaka factors" in multiple somatic cells. However, the procedure to get access to donor cells is hard or invasive in most cases. Hereon, we depict a stepwise method developed in our laboratory for the generation of iPSCs from renal epithelial cells present in urine, which is noninvasive, nonintegrating, and universal. The resulting urinary iPSCs (UiPSCs) exhibit pluripotent characteristics resemble embryonic stem cells (ESCs) and thus urine may be a favorable source for generating iPSCs.
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http://dx.doi.org/10.1007/7651_2021_419DOI Listing
October 2021

Sacubitril/Valsartan Alleviates Experimental Autoimmune Myocarditis by Inhibiting Th17 Cell Differentiation Independently of the NLRP3 Inflammasome Pathway.

Front Pharmacol 2021 15;12:727838. Epub 2021 Sep 15.

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Sacubitril/valsartan (Sac/Val) is a recently approved drug that is commonly used for treatment of heart failure. Several studies indicated that Sac/Val also regulated the secretion of inflammatory factors. However, the effect and mechanism of this drug modulation of inflammatory immune responses are uncertain. In this study, an experimental autoimmune myocarditis (EAM) mouse model was established by injection of α-myosin-heavy chain peptides. The effect of oral Sac/Val on EAM was evaluated by histological staining of heart tissues, measurements of cardiac troponin T and inflammatory markers (IL-6 and hsCRP). The effects of Sac/Val on NLRP3 inflammasome activation and Th1/Th17 cell differentiation were also determined. To further explore the signaling pathways, the expressions of cardiac soluble guanylyl cyclase (sGC) and NF-κB p65 were investigated. The results showed that Sac/Val downregulated the inflammatory response and attenuated the severity of EAM, but did not influence NLRP3 inflammasomes activation. Moreover, Sac/Val treatment inhibited cardiac Th17 cell differentiation, and this might be associated with sGC/NF-κB p65 signaling pathway. These findings indicate the potential use of Sac/Val for treatment of myocarditis.
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http://dx.doi.org/10.3389/fphar.2021.727838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479108PMC
September 2021

Systematic comparisons of dissolving and swelling hyaluronic acid microneedles in transdermal drug delivery.

Int J Biol Macromol 2021 Sep 28;191:783-791. Epub 2021 Sep 28.

College of Marine Life Science, Ocean University of China, 5 Yushan Road, 266003 Qingdao, China. Electronic address:

Transdermal drug delivery efficacy of hyaluronic acid dissolving microneedles (HA DMNs) is limited by low loading dose and poor drug condensation in needles. HA swelling MNs (HA SMNs) could improve the efficacy, but comparisons between the formulations is missing. In this work, DMNs and SMNs were fabricated of HA and methacrylated HA, respectively. Their properties of transdermal drug delivery were systematically compared. HA SMNs exhibited enhanced mechanical strength, fast swelling performance, and extended duration of microchannels in skin. The doxorubicin (DOX) loaded by one-step loading protocol in needles and baseplate of SMNs could be transdermally delivered through the diffusing path mediated by swollen needles, conquering the limit of poor drug condensation in DMNs needles and generated a longer Tmax but higher Cmax. The relative bioavailability of DOX/SMNs towards DOX/DMNs was 200% within 12 h. The results provide theoretical references for the application of HA MNs mediated transdermal drug delivery.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.09.161DOI Listing
September 2021

Bio-orthogonal Red and Far-Red Fluorogenic Probes for Wash-Free Live-Cell and Super-resolution Microscopy.

ACS Cent Sci 2021 Sep 20;7(9):1561-1571. Epub 2021 Aug 20.

Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.

Small-molecule fluorophores enable the observation of biomolecules in their native context with fluorescence microscopy. Specific labeling via bio-orthogonal tetrazine chemistry combines minimal label size with rapid labeling kinetics. At the same time, fluorogenic tetrazine-dye conjugates exhibit efficient quenching of dyes prior to target binding. However, live-cell compatible long-wavelength fluorophores with strong fluorogenicity have been difficult to realize. Here, we report close proximity tetrazine-dye conjugates with minimal distance between tetrazine and the fluorophore. Two synthetic routes give access to a series of cell-permeable and -impermeable dyes including highly fluorogenic far-red emitting derivatives with electron exchange as the dominant excited-state quenching mechanism. We demonstrate their potential for live-cell imaging in combination with unnatural amino acids, wash-free multicolor and super-resolution STED, and SOFI imaging. These dyes pave the way for advanced fluorescence imaging of biomolecules with minimal label size.
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http://dx.doi.org/10.1021/acscentsci.1c00703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461766PMC
September 2021

Several anthropometric measurements and cancer mortality: predictor screening, threshold determination, and joint analysis in a multicenter cohort of 12138 adults.

Eur J Clin Nutr 2021 Sep 28. Epub 2021 Sep 28.

Department of Gastrointestinal Surgery and Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.

Background: Anthropometric measurements (AMs) are cost-effective surrogates for evaluating body size. This study aimed to identify the optimal prognostic AMs, their thresholds, and their joint associations with cancer mortality.

Methods: We performed an observational cohort study including 12138 patients with cancer at five institutions in China. Information on demographics, disease, nutritional status, and AMs, including the body mass index, mid-arm muscle circumference, mid-arm circumference, handgrip strength, calf circumference (CC), and triceps-skinfold thickness (TSF), was collected and screened as mortality predictors. The optimal stratification was used to determine the thresholds to categorize those prognostic AMs, and their associations with mortality were estimated independently and jointly by calculating multivariable-adjusted hazard ratios (HRs).

Results: The study included 5744 females and 6394 males with a mean age of 56.9 years. The CC and TSF were identified as better mortality predictors than other AMs. The optimal thresholds were women 30 cm and men 32.8 cm for the CC, and women 21.8 mm and men 13.6 mm for the TSF. Patients in the low CC or low TSF group had a 13% (HR = 1.13, 95% CI = 1.03-1.23) and 22% (HR = 1.22, 95% CI = 1.12-1.32) greater mortality risk compared with their normal CC/TSF counterparties, respectively. Concurrent low CC and low TSF showed potential joint effect on mortality risk (HR = 1.39, 95% CI = 1.25-1.55).

Conclusions: These findings support the importance of assessing the CC and TSF simultaneously in hospitalized cancer patients to guide interventions to optimize their long-term outcomes.
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http://dx.doi.org/10.1038/s41430-021-01009-xDOI Listing
September 2021

The influences of electric field intensity and driving force on the slip behaviour of water flow in a nanochannel.

PLoS One 2021 22;16(9):e0257589. Epub 2021 Sep 22.

Jilin Provincial Key Laboratory for Numerical Simulation, Jilin Normal University, Siping, Jilin, P. R. China.

In the present work, non-equilibrium molecular dynamics (MD) simulations are used to investigate the flow of liquid water between two metallic solid atomistic smooth walls. The present work focuses on the combined effect of external electric field and driving force on the slip behaviour and structure of liquid water at the solid-water interface. The upper wall of the set model is positively charged, and the lower wall of the model is negatively charged. The simulation results show that as the driving force increases, the slip length also increases. At a given driving force, no matter how the electric field intensity changes, there is almost no change in the slip length, so the slip length is independent of the electric field strength. In addition, the results found that there is a linear relationship between the slip length and the normalised main peak of the static structure factor under different driving forces.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257589PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457446PMC
September 2021

Correlation of Platelet and Coagulation Function with Blood Stasis Syndrome in Coronary Heart Disease: A Systematic Review and Meta-Analysis.

Chin J Integr Med 2021 Sep 16. Epub 2021 Sep 16.

Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.

Objective: To investigate the correlation of platelet and coagulation function with blood stasis syndrome (BSS) in coronary heart disease (CHD).

Methods: The protocol for this meta-analysis was registered on PROSPERO (CRD42019129452). PubMed, Excerpta Medica Database (Embase), the Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched from inception to 1st June, 2020. Trials were considered eligible if they enrolled BSS and non-BSS (NBSS) patients with CHD and provided information on platelet and coagulation function. The platelet function, coagulation function, and fibrinolytic activity were compared between the BSS and NBSS groups. Forest plots were generated to show the SMDs or ESs with corresponding 95% CIs for each study. Subgroup analysis and sensitivity analysis were performed to explore potential sources of heterogeneity.

Results: The systematic search identified 1,583 articles. Thirty trials involving 10,323 patients were included in the meta-analysis. The results showed that mean platelet volume, platelet distribution width, platelet aggregation rate, platelet P selectin, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), thromboxane B2 (TXB2), 6-keto-prostaglandin F1alpha (6-keto-PGF1 α), and TXB2/6-keto-PGF1 α were higher in the BSS group than in the NBSS group (P<0.05 or P<0.01). Activated partial thromboplastin time was lower in the BSS group than in the NBSS group in the acute phase of CHD (P<0.01). The R and K values in thromboelastography and tissue plasminogen activator (t-PA) and t-PA/PAI-1 were lower in the BSS group than in the NBSS group (all P<0.01). No difference was found in the results of platelet count, plateletcrit, maximum amplitude, von Willebrand factor, prothrombin time, thrombin time, international normalized ratio, etc. between groups.

Conclusions: Increased platelet function, hypercoagulability, and decreased fibrinolytic activity were found among CHD patients with BSS.
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http://dx.doi.org/10.1007/s11655-021-2871-2DOI Listing
September 2021

Characterization of m6A-Related Genes Landscape in Skin Cutaneous Melanoma to Aid Immunotherapy and Assess Prognosis.

Int J Gen Med 2021 7;14:5345-5361. Epub 2021 Sep 7.

Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China.

Background: Skin cutaneous melanoma (SKCM) is the most malignant tumor among skin cancers. Immunotherapy has shown a great role in the advantageous prognosis of SKCM. However, only a small percentage of people can benefit from immunotherapy. To date, there has been insufficient evidence to reveal the prognostic value of m6A in SKCM and its relationship with the infiltration of immune cells and the efficacy of immunotherapy.

Methods: Here, we synthetically analyzed 23 m6A regulators from SKCM samples collected from the TCGA and GEO databases. We defined three m6A modification patterns and constructed m6A scores using principal component analysis (PCA).

Results: We found significant differences in overall survival (OS) and immune infiltration between different m6A subclusters. Besides, m6A score was positively correlated with regulatory T-cell and helper T-cell content, which may account for the association of high m6A scores with superior prognosis. Multivariate Cox regression analysis revealed that the m6A score was an independent prognostic indicator. Moreover, patients with high m6A scores showed a better response to immunotherapy, and this result was further validated in two independent immunotherapy cohorts receiving anti-PD-1/PD-L1 therapy.

Conclusion: The findings suggested the m6A score can screen suitable candidates for immunotherapy and can predict immunotherapy response. This analysis of different m6A patterns in a large sample of SKCM expanded our understanding of TME and provided new ideas for prognostic assessment and personalized immunotherapy strategies for SKCM patients.
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http://dx.doi.org/10.2147/IJGM.S328522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434882PMC
September 2021

Latinos' Conceptualization of Depression, Diabetes, and Mental Health-Related Stigma.

J Racial Ethn Health Disparities 2021 Sep 10. Epub 2021 Sep 10.

University of Texas Rio Grande Valley, School of Social Work, Edinburg, TX, USA.

Depression and diabetes are two of the most common health conditions experienced by those from Latino backgrounds. However, community-based stigma toward these health conditions may discourage those experiencing symptoms of depression or diabetes from seeking professional assistance. To assess stigma in the Latino community toward these common health conditions, a community-based sample of 469 Latino participants in a major urban area in the [Southwestern United States - Houston, TX] completed a face-to-face survey using an experimental vignette methodology. Participants were asked to name the problem that the subject of the vignette was experiencing based on the symptoms described in the vignette. This survey also inquired about public stigma toward individuals experiencing symptoms of depression and/or diabetes. Results indicate that although the majority (60%) of the sample were able to correctly identify symptoms of depression, it was more difficult for them to identify symptoms of depression with co-occurring diabetes. Overall levels of public stigma toward those experiencing depression were moderate, and co-occurring symptoms of diabetes did not moderate stigma toward those experiencing depression. These findings indicate a need for intervention approaches within the Latino community to increase health literacy related to depression and type 2 diabetes, as well as an ongoing need to reduce stigma toward those experiencing symptoms of depression. Implications for future research, practice, and health promotion are discussed.
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http://dx.doi.org/10.1007/s40615-021-01129-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432279PMC
September 2021

Low-Dose CT Image Denoising with Improving WGAN and Hybrid Loss Function.

Comput Math Methods Med 2021 26;2021:2973108. Epub 2021 Aug 26.

Computer Science and Technology, Changchun University of Science and Technology, Changchun 130022, China.

The X-ray radiation from computed tomography (CT) brought us the potential risk. Simply decreasing the dose makes the CT images noisy and diagnostic performance compromised. Here, we develop a novel denoising low-dose CT image method. Our framework is based on an improved generative adversarial network coupling with the hybrid loss function, including the adversarial loss, perceptual loss, sharpness loss, and structural similarity loss. Among the loss function terms, perceptual loss and structural similarity loss are made use of to preserve textural details, and sharpness loss can make reconstruction images clear. The adversarial loss can sharp the boundary regions. The results of experiments show the proposed method can effectively remove noise and artifacts better than the state-of-the-art methods in the aspects of the visual effect, the quantitative measurements, and the texture details.
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http://dx.doi.org/10.1155/2021/2973108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416402PMC
August 2021

Tooth biomarkers to characterize the temporal dynamics of the fetal and early-life exposome.

Environ Int 2021 12 2;157:106849. Epub 2021 Sep 2.

Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address:

Background: Teeth have unique histology that make this biomatrix a time-capsule for retrospective exposure analysis of fetal and early life. However, most analytic methods require pulverizing the whole tooth, which eliminates exposure timing information. Further, the range of chemicals and endogenous exposures that can be measured in teeth has yet to be fully characterized.

Methods: We performed untargeted metabolomics on micro-dissected layers from naturally shed deciduous teeth. Using four liquid-chromatography high-resolution mass spectrometry analytical modes, we profiled small molecules (<1000 Da) from prenatal and postnatal tooth fractions. In addition, we employed linear regression on the tooth fraction pairs from 31 children to identify metabolites that discriminate between prenatal and postnatal exposures.

Results: Of over 10,000 features measured in teeth dentin, 390 unique compounds were annotated from 62 chemical classes. The class with the largest number of compounds was carboxylic acids and their derivatives (36%). Of the annotated exogenous metabolites (phthalates, parabens, perfluoroalkyl compounds, and cotinine) and endogenous metabolites (fatty acids, steroids, carnitines, amino acids, and others), 91 are linked to 256 health conditions through published literature. Differential analysis revealed 267 metabolites significantly different between the prenatal and the postnatal tooth fractions (adj. p-value < 0.05, Bonferroni correction), and 21 metabolites exclusive to the prenatal fraction.

Conclusions: The prenatal and early postnatal exposome revealed from dental biomarkers represents a broad range of endogenous and exogenous metabolites for a comprehensive characterization in environmental health research. Most importantly, this technology provides a direct window into fetal exposures that is not possible by maternal biomarkers. Indeed, we identified several metabolites exclusively in the prenatal fraction, suggesting unique fetal exposures that are markedly different to postnatal exposures. Expansion of databases that include tooth matrix metabolites will strengthen biological interpretation and shed light on exposures during gestation and early life that may be causally linked with later health conditions.
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http://dx.doi.org/10.1016/j.envint.2021.106849DOI Listing
December 2021

Combined computational and intracellular peptide library screening: towards a potent and selective Fra1 inhibitor.

RSC Chem Biol 2021 Apr 29;2(2):656-668. Epub 2021 Jan 29.

Department of Biology & Biochemistry, University of Bath Claverton Down Bath BA2 7AY UK +44 (0)1225386867.

To date, most research into the inhibition of oncogenic transcriptional regulator, Activator Protein 1 (AP-1), has focused on heterodimers of cJun and cFos. However, the Fra1 homologue remains an important cancer target. Here we describe library design coupled with computational and intracellular screening as an effective methodology to derive an antagonist that is selective for Fra1 relative to Jun counterparts. To do so the CAN computational tool was used to rapidly screen >75 million peptide library members, narrowing the library size by >99.8% to one accessible to intracellular PCA selection. The resulting 131 072-member library was predicted to contain high quality binders with both a high likelihood of target engagement, while simultaneously avoiding homodimerization and off-target interaction with Jun homologues. PCA screening was next performed to enrich those members that meet these criteria. In particular, optimization was achieved inclusion of options designed to generate the potential for compromised intermolecular contacts in both desired and non-desired species. This is an often-overlooked prerequisite in the conflicting design requirement of libraries that must be selective for their target in the context of a range of alternative potential interactions. Here we demonstrate that specificity is achieved a combination of both hydrophobic and electrostatic contacts as exhibited by the selected peptide (Fra1W). analysis of the desired Fra1-Fra1W interaction further validates high Fra1 affinity (917 nM) yet selective binding relative to Fra1W homodimers or affinity for cJun. The CAN → PCA based multidisciplinary approach provides a robust screening pipeline in generating target-specific hits, as well as new insight into rational peptide design in the search for novel bZIP family inhibitors.
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http://dx.doi.org/10.1039/d1cb00012hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341738PMC
April 2021

Trans-ethnic Meta-analysis of Interactions between Genetics and Early Life Socioeconomic Context on Memory Performance and Decline in Older Americans.

J Gerontol A Biol Sci Med Sci 2021 Aug 27. Epub 2021 Aug 27.

Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI.

Later life cognitive function is influenced by genetics as well as early- and later-life socioeconomic context. However, few studies have examined the interaction between genetics and early childhood factors. Using gene-based tests (iSKAT/iSKAT-O), we examined whether common and/or rare exonic variants in 39 gene regions previously associated with cognitive performance, dementia, and related traits had an interaction with childhood socioeconomic context (parental education and financial strain) on memory performance or decline in European ancestry (EA, N=10,468) and African ancestry (AA, N=2,252) participants from the Health and Retirement Study. Of the 39 genes, 22 in EA and 19 in AA had nominally significant interactions with at least one childhood socioeconomic measure on memory performance and/or decline; however, all but one (father's education by SLC24A4 in AA) were not significant after multiple testing correction (FDR <0.05). In trans-ethnic meta-analysis, two genes interacted with childhood socioeconomic context (FDR <0.05): mother's education by MS4A4A on memory performance, and father's education by SLC24A4 on memory decline. Both interactions remained significant (p<0.05) after adjusting for respondent's own educational attainment, APOE ε4 status, lifestyle factors, BMI, and comorbidities. For both interactions in EA and AA, the genetic effect was stronger in participants with low parental education. Examination of common and rare variants in genes discovered through GWAS shows that childhood context may interact with key gene regions to jointly impact later life memory function and decline. Genetic effects may be more salient for those with lower childhood socioeconomic status.
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http://dx.doi.org/10.1093/gerona/glab255DOI Listing
August 2021

Subsurface-Carbon-Induced Local Charge of Copper for an On-Surface Displacement Reaction.

Angew Chem Int Ed Engl 2021 Oct 21;60(43):23123-23127. Epub 2021 Sep 21.

School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, China.

Transition-metal carbides have sparked unprecedented enthusiasm as high-performance catalysts in recent years. Still, the catalytic properties of copper carbide remain unexplored. By introducing subsurface carbon to Cu(111), a displacement reaction of a proton in a carboxyl acid group with a single Cu atom is demonstrated at the atomic scale and room temperature. Its occurrence is attributed to the C-doping-induced local charge of surface Cu atoms (up to +0.30 e/atom), which accelerates the rate of on-surface deprotonation via reduction of the corresponding energy barrier, thus enabling the instant displacement of a proton with a Cu atom when the molecules adsorb on the surface. This well-defined and robust Cu surface based on subsurface-carbon doping offers a novel catalytic platform for on-surface synthesis.
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http://dx.doi.org/10.1002/anie.202108712DOI Listing
October 2021

Liraglutide Improves Endothelial Function via the mTOR Signaling Pathway.

J Diabetes Res 2021 16;2021:2936667. Epub 2021 Aug 16.

Department of Endocrinology, Key Laboratory of Endocrinology, National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.

Background: Mammalian target of rapamycin (mTOR) is crucial for endothelial function. This study is aimed at assessing whether the glucagon-like peptide-1 (GLP-1) analogue liraglutide has a protective effect on endothelial function via the mTOR signaling pathway.

Methods: Human umbilical vein endothelial cells (HUVECs) were administered liraglutide (100 nM) for 0, 10, 30, 60, 720, and 1440 minutes, respectively. Then, the expression and phosphorylation levels of mTOR, mTOR-Raptor complex (mTORC1), and mTOR-Rictor complex (mTORC2) were determined by Western blot and immunoprecipitation, while mTORC1 and mTORC2 expression was blocked by siRNA-Raptor and siRNA-Rictor, respectively. Akt phosphorylation was detected by Western blot. HUVECs were then incubated with liraglutide in the absence or presence of Akt inhibitor IV. Nitric oxide (NO) release was assessed by the nitrate reductase method. Phosphorylated endothelial nitric oxide synthase (eNOS), human telomerase reverse transcriptase (hTERT), and apoptosis-related effectors were assessed for protein levels by Western blot. Telomerase activity was evaluated by ELISA.

Results: Sustained mTOR phosphorylation, mTORC2 formation, and mTORC2-dependent Akt phosphorylation were induced by liraglutide. In addition, eNOS phosphorylation, NO production, nuclear hTERT accumulation, and nuclear telomerase activity were enhanced by mTORC2-mediated Akt activation. Liraglutide also showed an antiapoptotic effect by upregulating antiapoptotic proteins and downregulating proapoptotic proteins in an mTORC2-Akt activation-dependent manner.

Conclusion: Liraglutide significantly improves endothelial function, at least partially via the mTORC2/Akt signaling pathway.
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http://dx.doi.org/10.1155/2021/2936667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384515PMC
August 2021

Preclinical Pharmacokinetics, Tissue Distribution, and Primary Safety Evaluation of Indo5, a Novel Selective Inhibitor of c-Met and Trks.

Front Pharmacol 2021 10;12:711126. Epub 2021 Aug 10.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China.

The compound [3-(1H-benzimidazol-2-methylene)-5-(2-methylphenylaminosulfo)-2-indolone], known as Indo5, is a novel selective inhibitor of c-Met and Trks, and it is a promising anticancer candidate against hepatocellular carcinoma (HCC). Assessing the pharmacokinetic properties, tissue distribution, and toxicity of Indo5 is critical for its medicinal evaluation. A series of sensitive and specific liquid chromatography-tandem mass spectrometry methods were developed and validated to determine the concentration of Indo5 in rat plasma and tissue homogenates. These methods were then applied to investigate the pharmacokinetics and tissue distribution of Indo5 in rats. After intravenous injection of Indo5, the maximum concentration (C) and the time at which C was reached (T) were 1,565.3 ± 286.2 ng/ml and 1 min, respectively. After oral administration, C and T were 54.7 ± 10.4 ng/ml and 2.0 ± 0.48 h, respectively. We calculated the absolute oral bioavailability of Indo5 in rats to be 1.59%. Following intravenous injection, the concentrations of Indo5 in various tissues showed the following order: liver > kidney ≈ heart > lung ≈ large intestine ≈ small intestine ≈ stomach > spleen > brain ≈ testes; hence, Indo5 distributed highest in the liver and could not cross the blood-brain or blood-testes barriers. Continuous injection of Indo5 for 21 days did not lead to liver injury, considering unchanged ALT and AST levels, normal histological architecture of the liver, and normal number and frequencies of immune cells in the liver, indicating a very low toxicity of Indo5 . Collectively, our findings provide a comprehensive understanding of the biological actions of Indo5 its development as an antitumor treatment for HCC patients.
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http://dx.doi.org/10.3389/fphar.2021.711126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383318PMC
August 2021

SnapHiC: a computational pipeline to identify chromatin loops from single-cell Hi-C data.

Nat Methods 2021 09 26;18(9):1056-1059. Epub 2021 Aug 26.

Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.

Single-cell Hi-C (scHi-C) analysis has been increasingly used to map chromatin architecture in diverse tissue contexts, but computational tools to define chromatin loops at high resolution from scHi-C data are still lacking. Here, we describe Single-Nucleus Analysis Pipeline for Hi-C (SnapHiC), a method that can identify chromatin loops at high resolution and accuracy from scHi-C data. Using scHi-C data from 742 mouse embryonic stem cells, we benchmark SnapHiC against a number of computational tools developed for mapping chromatin loops and interactions from bulk Hi-C. We further demonstrate its use by analyzing single-nucleus methyl-3C-seq data from 2,869 human prefrontal cortical cells, which uncovers cell type-specific chromatin loops and predicts putative target genes for noncoding sequence variants associated with neuropsychiatric disorders. Our results indicate that SnapHiC could facilitate the analysis of cell type-specific chromatin architecture and gene regulatory programs in complex tissues.
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http://dx.doi.org/10.1038/s41592-021-01231-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440170PMC
September 2021

Mental Health Promotion and Stigma Reduction Among University Students Using the Reach, Efficacy, Adoption, Implementation, and Maintenance (RE-AIM) Framework: Protocol for a Mixed Methods Study.

JMIR Res Protoc 2021 Aug 26;10(8):e25592. Epub 2021 Aug 26.

Daphne Cockwell School of Nursing, Ryerson University, Toronto, ON, Canada.

Background: Rapid urbanization, academic pressures, and developmental life transition stressors contribute to mental health stress for postsecondary students in China. Effective prevention, early identification, and timely intervention are challenged by stigma, a lack of mental health literacy, and inadequate mental health resources.

Objective: Our implementation science (IS) research project is aimed at evaluating the use of an evidence-informed mental health promotion intervention named Acceptance and Commitment to Empowerment - Linking Youth and 'Xin' (hearts) (ACE-LYNX) to promote university student mental health in Jinan, China.

Methods: We will engage and collaborate with Shandong Mental Health Center, the provincial mental health center, and six local universities in different regions of Jinan. The ACE-LYNX intervention aims to reduce social stigma against mental illness, enhance mental health literacy, and improve access to quality mental health care by increasing interdisciplinary collaboration and forming a mental health network. It is based on two evidence-based approaches, Acceptance and Commitment Therapy (ACT) and Group Empowerment Psychoeducation (GEP), and it will be delivered through online learning and in-person group training. The project will train 90 interdisciplinary professionals using the model. They will in turn train 15 professionals and 20 students at each university. The project will adopt the Reach, Efficacy, Adoption, Implementation, and Maintenance (RE-AIM) framework, which provides a structure to examine the process and outcomes of implementation using mixed methods comprising quantitative and qualitative approaches along five dimensions: reach, efficacy, adoption, implementation, and maintenance.

Results: Over the course of the project, 720 champions will be directly trained. They will contribute to developing a formal and informal mental health network, strengthened by student-led mental health initiatives and professional-led initiatives to promote collaborative care and facilitated care pathways. We anticipate that our project will reach out to 11,000 to 18,000 students.

Conclusions: This IS protocol will outline our unique intervention model and key steps to contextualize, implement, and evaluate community-based mental health intervention.

International Registered Report Identifier (irrid): PRR1-10.2196/25592.
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http://dx.doi.org/10.2196/25592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430866PMC
August 2021

Mitochondrial calcium uniporter promotes cell proliferation and migration in esophageal cancer.

Oncol Lett 2021 Sep 28;22(3):686. Epub 2021 Jul 28.

Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, P.R. China.

Increasing evidence has suggested that mitochondrial calcium uniporter (MCU) is involved in various types of cancer. However, its functions remain unclear in esophageal cancer. The aim of the present study was to explore its abnormal expression and clinical implications in esophageal cancer. A total of 110 patients with esophageal cancer were enrolled in the study. Western blotting was performed to examine the protein expression levels of MCU in 8 pairs of esophageal cancer and adjacent normal tissues. Using immunochemistry, a total of 110 esophageal cancer specimens were analyzed to identify the association between MCU expression and clinicopathological features of patients with esophageal cancer. Furthermore, immunofluorescence of MCU was performed. Pearson's correlation analysis was performed between MCU and hypoxia inducible factor (HIF)-1α/VEGF/E-cadherin/Vimentin expression based on western blotting. After KYSE-150 and TE-1 cells were treated with the MCU agonist Spermine and a small interfering RNA against MCU (si-MCU), a series of functional assays were performed, including Cell Counting Kit-8, colony formation and Transwell assays. The results revealed that, compared with in adjacent normal tissues, MCU was highly expressed in esophageal cancer tissues. MCU expression was significantly associated with depth of invasion, lymph node metastasis, TNM stage and distant metastasis. Moreover, MCU was significantly correlated with HIF-1α/VEGF/E-cadherin/Vimentin in esophageal cancer tissues. MCU overexpression promoted VEGF, MMP2, Vimentin and N-cadherin expression, while it inhibited E-cadherin expression in KYSE-150 and TE-1 cells, and opposite results were observed after transfection with si-MCU. Furthermore, MCU overexpression accelerated the proliferation and migration of KYSE-150 and TE-1 cells. Thus, the current findings suggested that high MCU expression may participate in cell proliferation, migration and epithelial-mesenchymal transition in esophageal cancer.
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http://dx.doi.org/10.3892/ol.2021.12947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335723PMC
September 2021

Early life exposure to air pollution and cell-mediated immune responses in preschoolers.

Chemosphere 2021 Aug 20;286(Pt 3):131963. Epub 2021 Aug 20.

Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China; Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA. Electronic address:

Background: Exposure to air pollution has been linked with altered immune function in adults, but little is known about its effects on early life. This study aimed to investigate the effects of exposure to air pollution during prenatal and postnatal windows on cell-mediated immune function in preschoolers.

Methods: Pre-school aged children (2.9 ± 0.5 y old, n = 391) were recruited from a mother-child cohort study in Wuhan, China. We used a spatial-temporal land use regression (LUR) model to estimate exposures of particulate matter with aerodynamic diameters ≤2.5 μm (PM) and ≤10 μm (PM), and nitrogen dioxide (NO) during the specific trimesters of pregnancy and the first two postnatal years. We measured peripheral blood T lymphocyte subsets and plasma cytokines as indicators of cellular immune function. We used multiple informant models to examine the associations of prenatal and postnatal exposures to air pollution with cell-mediated immune function.

Results: Prenatal exposures to PM, PM, and NO during early pregnancy were negatively associated with %CD3 and %CD3CD8 cells, and during late pregnancy were positively associated with %CD3 cells. Postnatal exposures to these air pollutants during 1-y or 2-y childhood were positively associated with IL-4, IL-5, IL-6, and TNF-α. We also observed that the associations of prenatal or postnatal air pollution exposures with cellular immune responses varied by child's sex.

Conclusions: Our results suggest that exposure to air pollution during different critical windows of early life may differentially alter cellular immune responses, and these effects appear to be sex-specific.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131963DOI Listing
August 2021

Enhancing social support and knowledge perception decreases patient delay in breast cancer.

Gland Surg 2021 Jul;10(7):2220-2231

Department of Breast Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Background: Patient delay commonly appears in breast cancer (BC), but the findings for influential factors may be contaminated by recall bias. The real factors in patient delay (divided into appraisal delay and utilization delay) for women with BC urgently need to be objectively analyzed for preventing the progression of this disease.

Methods: Women meeting strict inclusion and exclusion criteria were asked to fill in a questionnaire, which included three sections of sociodemographic characteristics, medical history, and knowledge of BC. Later on, the outcomes were processed according to the verification of BC by pathological diagnosis. Then, multiple linear regression was conducted to analyze the potential factors of the delay and to explore their relations between these factors and BC.

Results: Appraisal delay is the leading component of patient delay. Appraisal delay's time distribution of a higher percentage at delay time 0-29 and >360 days, while other delay time occupies lower percentage, which is highly consistent with that of patient delay, while utilization delay mainly occurs in the 0-29 days period. Concerning the influential factors for the different phases of delay, age (P=0.051, P=0.035 separately in appraisal and patient delay), residential address (P=0.036, P=0.010) and symptom disclosure to others (P=0.015, P=0.015) led to a decrease of appraisal and patient delay. However, reasons for first medical consultation (P=0.033, P=0.006) and knowledge of BC (P=0.027, P=0.002) would accelerate appraisal and patient delay. Many factors related to hospitals, such as hospital category for first medical consultation (P=0.030) and examinations for first medical consultation (P=0.055) would reduce utilization delay.

Conclusions: Obstacles in medical consultation for younger women should be removed, and early interventions are needed to avoid progression of BC.
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http://dx.doi.org/10.21037/gs-21-227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340337PMC
July 2021

Rivaroxaban versus Vitamin K Antagonists (warfarin) based on the triple therapy for left ventricular thrombus after ST-Elevation myocardial infarction.

Heart Vessels 2021 Aug 22. Epub 2021 Aug 22.

Department of Cardiology, China-Japan Union Hospital of Jilin University, Jilin Provincial Molecular Biology Research Center for Precision Medicine of Major Cardiovascular Disease, Xiantai Street NO.126, Changchun, China.

Background: Left ventricular thrombus (LVT) can complicate ST-Elevation myocardial infarction (STEMI) and is associated with poor outcomes. Conventional triple anticoagulation [Vitamin K Antagonists (VKA) plus dual-antiplatelet therapy (DAPT)] is the first-line therapy for LVT after STEMI. In patients with LVT following STEMI, contemporary data of triple therapy with rivaroxaban are lacking.

Methods: We conducted a retrospective cohort study involving 1335 STEMI patients who underwent primary percutaneous coronary intervention (PCI). Among patients who developed LVT after STEMI, we observed differences in efficacy between rivaroxaban plus DAPT therapy and VKA plus DAPT. The time of LVT resolution was also evaluated, as well as net clinical adverse events, and rates of bleeding events.

Results: In 1335 patients with STEMI, a total of 77 (5.7%) developed LVT over the follow-up period (median 25.0 months). Of the patients diagnosed with LVT, 31 patients were started on triple therapy with VKA, 33 patients on triple therapy with rivaroxaban. There was a consistent similarity in LVT resolution with rivaroxaban application compared to VKA application during the follow-up period [HR (log-rank test) 1.57(95% CI 0.89-2.77), p = 0.096; Adjusted HR 1.70(95% CI 0.90-3.22), p = 0.104]. Triple therapy with rivaroxaban showed quicker resolution than with VKA (6 months: p = 0.049; 12 months: p = 0.044; 18 months: p = 0.045). Similar risks of ISTH bleeding were not significantly different between the 2 groups [VKA 9.7% vs Rivaroxaban 6.1%, Adjusted HR 0.48 (95% CI 0.73-3.20); p = 0.444)]. Fewer net adverse clinical events (NACE) were observed in the rivaroxaban group [VKA 58.1% vs Rivaroxaban 24.2%; HR (log-rank test) 0.31(95% CI 0.14-0.68), p = 0.003; Adjusted HR 0.23(95% CI 0.09-0.57), p = 0.001].

Conclusion: In the observational study, triple therapy with rivaroxaban has similar and quicker LVT resolution in patients with LVT after STEMI, compared with triple therapy with VKA, and perhaps was associated with a better clinical benefit. Larger sample sizes and randomized controlled trials are needed to confirm this observation.
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http://dx.doi.org/10.1007/s00380-021-01921-zDOI Listing
August 2021

Efficacy of Tripterygium wilfordii Hook F on animal model of Diabetic Kidney Diseases: A systematic review and meta-analysis.

J Ethnopharmacol 2021 Dec 19;281:114536. Epub 2021 Aug 19.

Endocrinology Department, First Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130021, China. Electronic address:

Ethnopharmacological Relevance: Tripterygium wilfordii Hook F (TwHF) has been clinically applied in the treatment of Diabetic Kidney Diseases (DKD). A large number of animal experiments focused on the TwHF treatment of DKD were conducted every year, but the evidence for these preclinical studies is unclear.

Aim Of The Study: This study aims to evaluate the efficacy of TwHF on diabetic nephropathy through a stematic reviews and meta-analysis of animal models, and whether it has an effect on improving kidney pathology, renal function indicators and blood sugar levels, it also summarizes the use of TwHF for treatment the underlying mechanism of DKD.

Materials And Methods: We systematically searched studies from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang database from inception to May 2020. Chinese studies from the list of Chinese Core Journals would be included. SYRCLE's risk of bias tool for animal studies was applied to assess the methodological quality of studies. A meta-analysis was performed by using RevMan 5.3.

Results: Out of 429 records identified in the initial search, 32 studies were selected. The results indicated that, compared with control group, TwHF treatment improved 24 h urine protein (24 h-UP) level (SMD - 4.21, 95% CI - 5.38 to - 3.04, P < 0.001), serum creatinine (Scr) (MD - 14.97, 95% CI - 20.42 to - 9.53, P < 0.001), blood urea nitrogen (BUN) (MD - 4.07, 95% CI - 5.49 to - 2.66, P < 0.001), blood glucose (Glu) (MD - 2.40, 95% CI - 4.304 to - 0.49, P = 0.01), Triglyceride (TG) (MD - 1.57, 95% CI - 2.06 to - 1.08, P < 0.001), and Cholesterol (TC) (MD - 1.49, 95% CI - 2.23 to - 0.75 P < 0.001); and increased the level of albumin (Alb) (MD 3.40, 95% CI 1.69 to 5.11, P < 0.001) and weight (MD 30.89, 95% CI 24.35 to 37.42, P < 0.001). There were no statistical difference on Alanine aminotransferase (ALT) (MD 3.00, 95% CI - 7.80 to 13.81, P = 0.59) and Aspartate aminotransferase (AST) (MD 0.77, 95% CI -15.05 to 16.60, P = 0.92) after TwHF. Meta regression analysis showed that the DKD model induced by different methods (type I/II), the dose of Tripterygium wilfordii and the intervention time were not the reasons for the heterogeneity of 24 h-UP, Alb, Glu, Scr, and BUN (p > 0.05).

Conclusions: TwHF is an effective and safe to treat DKD, which can protect the kidneys through anti-inflammation, improving oxidative stress and podocyte damage, and inhibiting mesangial cell proliferation and extracellular matrix proliferation.
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http://dx.doi.org/10.1016/j.jep.2021.114536DOI Listing
December 2021
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