Publications by authors named "Ying Shen"

663 Publications

The 90% Effective Dose of Sufentanil for Epidural Analgesia in the Early First Stage of Labor: A Double-blind, Sequential Dose-Finding Study.

Clin Ther 2021 Jun 7. Epub 2021 Jun 7.

Department of Anesthesiology, the International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China. Electronic address:

Purpose: Epidural analgesia in the latent phase of the first stage of labor has been recognized and accepted by anesthesiologists worldwide. However, there is no unified consensus on the exact dosage of sufentanil with the combination of ropivacaine in the induction of epidural analgesia in the early first stage of labor. In this sequential dose-finding study, the 90% effective dose (ED) of sufentanil for epidural administration in the early first stage of labor was estimated to minimize the adverse effects of using higher doses.

Methods: Forty parturients with cervical dilatation of 2 to 4 cm who requested epidural analgesia were enrolled in this study. Parturients received 15 mL of a combination of ropivacaine 13 mg and the test dose of sufentanil. The initial dose of sufentanil in epidural administration was 1 μg, and the dose of sufentanil for the next parturient was based on the response of the preceding participant as per a biased coin up-and-down design. The primary outcome was the dose of sufentanil that resulted in successful epidural administration by maintaining the parturients' visual analog scale scores at ≤30 mm in the first 15, 30, and 45 minutes of induction. The ED and 95% CIs were estimated using isotonic regression methods and bootstrapping.

Findings: The estimated ED of sufentanil in epidural administration in the early first stage of labor was 1.91 μg (95% CI, 1.82-2.35 μg) in this sequential dose-finding study.

Implications: Sufentanil at a dosage of 2 μg is recommended for the administration of epidural analgesia in parturients in the early first stage of labor. ChiCTR.org.cn identifier: 1900021683.
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http://dx.doi.org/10.1016/j.clinthera.2021.05.002DOI Listing
June 2021

Evaluation of a high-performance liquid chromatography method for urinary oxalate determination and investigation regarding the pediatric reference interval of spot urinary oxalate to creatinine ratio for screening of primary hyperoxaluria.

J Clin Lab Anal 2021 Jun 7:e23870. Epub 2021 Jun 7.

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Urinary oxalate can provide important clues for the screening and monitoring of children with primary hyperoxaluria (PH), which is a potentially life-threatening condition. However, little effort has been devoted to improve the oxalate assay in recent years. We have proposed a reliable and cost-effective high-performance liquid chromatography (HPLC) method for urinary oxalate determination.

Methods: Urine specimens were centrifuged after one-step derivatization, and the supernatants were subjected to HPLC analysis.

Results: The method was validated with consistent linearity from 0.0625 to 2.0 mmol/L with coefficients of variation ≤7.73%, good recovery, low carryover, satisfactory sample stability, and analytical specificity. The lower limit of quantification and the limit of detection were 0.03130 and 0.0156 mmol/L, respectively. Imprecision values were ≤2.92% and ≤16.6% for externally and internally produced controls, respectively. The pediatric reference interval of spot urinary oxalate to creatinine ratios was established together with its application in screening of PH in patients with renal diseases, revealing its successful deployment in our laboratory.

Conclusions: This reliable HPLC method could serve as a significant tool to determine urinary oxalate levels for screening and monitoring of children with PH in routine clinical laboratories.
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http://dx.doi.org/10.1002/jcla.23870DOI Listing
June 2021

PQBP1: A New Player in Metabotropic Glutamate Receptor Signaling and Synaptic Plasticity.

Authors:
Li-Da Su Ying Shen

Neurosci Bull 2021 Jun 6. Epub 2021 Jun 6.

Department of Physiology, Zhejiang University School of Medicine, Hangzhou, 310058, China.

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http://dx.doi.org/10.1007/s12264-021-00720-wDOI Listing
June 2021

Group 1 Metabotropic Glutamate Receptors in Neurological and Psychiatric Diseases: Mechanisms and Prospective.

Neuroscientist 2021 Jun 4:10738584211021018. Epub 2021 Jun 4.

Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China.

Metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors that are activated by glutamate in the central nervous system (CNS). Basically, mGluRs contribute to fine-tuning of synaptic efficacy and control the accuracy and sharpness of neurotransmission. Among eight subtypes, mGluR1 and mGluR5 belong to group 1 (Gp1) family, and are implicated in multiple CNS disorders, such as Alzheimer's disease, autism, Parkinson's disease, and so on. In the present review, we systematically discussed underlying mechanisms and prospective of Gp1 mGluRs in a group of neurological and psychiatric diseases, including Alzheimer's disease, Parkinson's disease, autism spectrum disorder, epilepsy, Huntington's disease, intellectual disability, Down's syndrome, Rett syndrome, attention-deficit hyperactivity disorder, addiction, anxiety, nociception, schizophrenia, and depression, in order to provide more insights into the therapeutic potential of Gp1 mGluRs.
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http://dx.doi.org/10.1177/10738584211021018DOI Listing
June 2021

Analysis of Differentiated Chemical Components between Zijuan Purple Tea and Yunkang Green Tea by UHPLC-Orbitrap-MS/MS Combined with Chemometrics.

Foods 2021 May 12;10(5). Epub 2021 May 12.

State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Sciences and Technology, Anhui Agricultural University, Hefei 230036, China.

Zijuan tea ( cv. Zijuan) is a unique purple tea. Recently, purple tea has drawn much attention for its special flavor and health benefits. However, the characteristic compounds of purple tea compared with green tea have not been reported yet. The present study employed a non-targeted metabolomics approach based on ultra-high performance liquid chromatography (UHPLC)-Orbitrap-tandem mass spectrometry (MS/MS) for comprehensive analysis of characteristic metabolites between Zijuan purple tea (ZJT) and Yunkang green tea (YKT). Partial least squares-discriminant analysis (PLS-DA) indicated that there are significant differences in chemical profiles between ZJT and YKT. A total of 66 major differential metabolites included catechins, proanthocyanins, flavonol and flavone glycosides, phenolic acids, amino acids and alkaloids were identified in ZJT. Among them, anthocyanins are the most characteristic metabolites. Nine glycosides of anthocyanins and six glycosides of proanthocyanins were found to be significantly higher in ZJT than that in YKT. Subsequently, pathway analysis revealed that ZJT might generate anthocyanins and proanthocyanins through the flavonol and flavone glycosides. Furthermore, quantitative analysis showed absolutely higher concentrations of total anthocyanins in ZJT, which correlated with the metabolomics results. This study presented the comprehensive chemical profiling and the characterized metabolites of ZJT. These results also provided chemical evidence for potential health functions of ZJT.
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http://dx.doi.org/10.3390/foods10051070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151513PMC
May 2021

Fabrication of Hydroxyapatite/Tantalum Composites by Pressureless Sintering in Different Atmosphere.

ACS Omega 2021 May 3;6(19):12831-12840. Epub 2021 May 3.

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, China.

The effect of sintering atmosphere (air and Ar) and temperature (1100, 1200, 1300 °C) on the microstructure, mechanical properties, and bioactivity of hydroxyapatite/tantalum (HA/Ta) composites were systematically investigated by pressureless sintering of the mixture of HA and Ta powders. It shows that the sintering atmosphere greatly impacts the phase composition and microstructure of the HA/Ta composites. The higher diffusion of atoms promotes shrinkage and causes deeper reaction fusion between the HA matrix and Ta, which improved the interfacial binding of the HA/Ta composites. The refined grain structure and improved interfacial binding obtained within the Ar atmosphere compared to the air atmosphere benefit the mechanical properties. The maximum bending strength and shrinkage observed for the composites sintered at 1300 °C in the Ar atmosphere are 27.24 MPa and 6.65%, respectively. The cell counting kit-8 (CCK-8) method was used to investigate the in vitro cytocompatibility of HA/Ta composites. The results revealed that the HA/Ta composites sintered with different conditions have no cytotoxicity. The simulated body fluid (SBF) soaking results showed that all of the studied composites possess desirable bioactivity, as demonstrated by their ability to form calcium-deficient carbonate apatite layer on the surfaces. For composites sintered at 1300 °C, the surface apatite layer coverage of the composites obtained in the Ar atmosphere was increased by 139.7% than the ones obtained in air, which confirmed an enhanced bioactive mineralization ability. The results indicated that the HA/Ta composites sintered at 1300 °C in Ar possess desirable mechanical properties and bioactivity. This work opens up the new possibility for preparing HA-based composites and is of great value in biomedical applications.
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http://dx.doi.org/10.1021/acsomega.1c01205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154243PMC
May 2021

Protein Phosphatase 2A Mediates YAP Activation in Endothelial Cells Upon VEGF Stimulation and Matrix Stiffness.

Front Cell Dev Biol 2021 13;9:675562. Epub 2021 May 13.

Laboratory of Molecular Ophthalmology, Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.

Angiogenesis is an essential process during development. Abnormal angiogenesis also contributes to many disease conditions such as tumor and retinal diseases. Previous studies have established the Hippo signaling pathway effector Yes-associated protein (YAP) as a crucial regulator of angiogenesis. In ECs, activated YAP promotes endothelial cell proliferation, migration and sprouting. YAP activity is regulated by vascular endothelial growth factor (VEGF) and mechanical cues such as extracellular matrix (ECM) stiffness. However, it is unclear how VEGF or ECM stiffness signal to YAP, especially how dephosphorylation of YAP occurs in response to VEGF stimulus or ECM stiffening. Here, we show that protein phosphatase 2A (PP2A) is required for this process. Blocking PP2A activity abolishes VEGF or ECM stiffening mediated YAP activation. Systemic administration of a PP2A inhibitor suppresses YAP activity in blood vessels in developmental and pathological angiogenesis mouse models. Consistently, PP2A inhibitor also inhibits sprouting angiogenesis. Mechanistically, PP2A directly interacts with YAP, and this interaction requires proper cytoskeleton dynamics. These findings identify PP2A as a crucial mediator of YAP activation in ECs and hence as an important regulator of angiogenesis.
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http://dx.doi.org/10.3389/fcell.2021.675562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158299PMC
May 2021

Effects of Virtual Reality Intervention on Cognition and Motor Function in Older Adults With Mild Cognitive Impairment or Dementia: A Systematic Review and Meta-Analysis.

Front Aging Neurosci 2021 5;13:586999. Epub 2021 May 5.

Department of Rehabilitation, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Virtual reality (VR) intervention is an innovative and efficient rehabilitative tool for patients affected by stroke, Parkinson's disease, and other neurological disorders. This meta-analysis aims to evaluate the effects of VR intervention on cognition and motor function in older adults with mild cognitive impairment or dementia. Seven databases were systematically searched for relevant articles published from inception to April 2020. Randomized controlled trials examining VR intervention in adults with mild cognitive impairment or dementia aged >60 years were included. The primary outcome of the study was cognitive function, including overall cognition, global cognition, attention, executive function, memory, and visuospatial ability. The secondary outcome was motor function, consisting of overall motor function, balance, and gait. A subgroup analysis was also performed based on study characteristics to identify the potential factors for heterogeneity. Eleven studies including 359 participants were included for final analysis. Primary analysis showed a significant moderate positive effect size (ES) of VR on overall cognition ( = 0.45; 95% confidence interval (CI) = 0.31-0.59; < 0.001), attention/execution ( = 0.49; 95% CI = 0.26-0.72; < 0.001), memory ( = 0.57; 95% CI = 0.29-0.85; < 0.001), and global cognition ( = 0.32; 95% CI = 0.06-0.58; = 0.02). Secondary analysis showed a significant small positive ES on overall motor function ( = 0.28; 95% CI = 0.05-0.51; = 0.018). The ES on balance ( = 0.43; 95% CI = 0.06-0.80; = 0.02) was significant and moderate. The ES on visuospatial ability and gait was not significant. In the subgroup analysis, heterogeneity was detected in type of immersion and population diagnosis. VR intervention is a beneficial non-pharmacological approach to improve cognitive and motor function in older adults with mild cognitive impairment or dementia, especially in attention/execution, memory, global cognition, and balance. VR intervention does not show superiority on visuospatial ability and gait performance.
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http://dx.doi.org/10.3389/fnagi.2021.586999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136286PMC
May 2021

Assessing the accuracy of visual blood loss estimation in postpartum hemorrhage in Shanghai hospitals: A web-based survey for nurses and midwives.

J Clin Nurs 2021 May 22. Epub 2021 May 22.

International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Aims And Objectives: This study aimed at evaluating the accuracy of visual estimated blood loss in postpartum haemorrhage by midwives and nurses, as well as exploring its influencing factors.

Background: Timely recognition of postpartum haemorrhage is critical in saving maternal lives. Yet midwives and nurses can barely distinguish whether the blood loss has reached a life-threatening amount without precise measurement. Understanding their ability to accurately estimate the amount of blood loss and the influencing factors can help improve this ability with effective measures.

Design: This research was a multicenter cross-sectional survey with convenient sampling.

Material And Methods: Using a modified online visual estimation questionnaire of blood loss, the QR code of this survey was sent to midwives and obstetrical nurses engaged in clinical practice in secondary and tertiary hospitals in Shanghai. A descriptive analysis was performed with demographics and the responses of visual estimated blood loss of each volume. The difference and consistency of the responses of each volume were evaluated. The relationship between each demographic characteristic and accuracy was explored. STROBE statement checklist was chosen for reporting the study process.

Results: A total of 361 midwives and nurses participated in the survey. The finding showed an overall accuracy of 30.52% (1763/5776), with 25.3% and 18.0% subjects distinguishing postpartum haemorrhage (500 ml) and severe postpartum haemorrhage (1000 ml), respectively. The Kappa coefficients were slight to moderate (0.037-0.590). There were no differences among the categories of gender, age, academic degree, position, title, working experience in years, working department and reported methods of blood loss estimation with regard to accuracy. However, having institutional guidance for blood loss calculation showed a significant relationship with higher accuracy.

Relevance To Clinical Practice: While representing a relatively well-developed area in China, the accuracy of visual estimated blood loss was not satisfactory, as suggested in other developed countries around the world. Training and institutional guidance on blood loss quantification should be provided in midwifery settings, regardless of how the level of medical development is advanced.

Conclusions: The accuracy of VEBL was low even with a visual aid, especially when the volume exceeds 500 ml. To improve accuracy, institutions should make standardadized assessment guidance and provide regular training for blood loss quantification.
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http://dx.doi.org/10.1111/jocn.15860DOI Listing
May 2021

Effectiveness of erenumab and onabotulinumtoxinA on acute medication usage and health care resource utilization as migraine prevention in the United States.

J Manag Care Spec Pharm 2021 May 17:1-14. Epub 2021 May 17.

Novartis Pharma AG, Basel, CH-4002, Switzerland.

Migraine is a common neurological disease that can have a substantial impact on patients' lives and on society. Erenumab, a fully human monoclonal antibody that targets the calcitonin gene-related peptide receptor, was specifically developed for migraine prevention. The efficacy of erenumab has been established in several clinical trials; however, the real-world comparative effectiveness of erenumab has not been fully investigated. To evaluate the real-world impact of erenumab and onabotulinumtoxinA on acute medication usage and health care resource utilization (HCRU) among patients with migraine in the United States. This retrospective US claims analysis (Optum's deidentified Clinformatics Data Mart Database) evaluated patients aged at least 18 years diagnosed with migraine who initiated erenumab or onabotulinumtoxinA between May 1, 2018, and September 30, 2019 (index date: first erenumab/onabotulinumtoxinA claim). Cohorts were matched 1:1 using the propensity score (PS) method (greedy match with caliper = 0.1). Stratification was performed based on gender, chronic migraine without aura diagnosis, onabotulinumtoxinA use, and acute/preventive drug use. The impact of erenumab and onabotulinumtoxinA on acute medication usage and HCRU was assessed in the 6-month post-index period. An exploratory analysis assessed the impact of erenumab and onabotulinumtoxinA on a composite endpoint of: (1) outpatient visit with a migraine diagnosis and associated acute medication claim, (2) hospital admission with a primary migraine diagnosis, or (3) emergency department visit with a primary migraine diagnosis. PS-matched data were used for comparative analyses; logistic regression with covariate adjustment was used for dichotomous variables, and a negative binomial model was used for count variables, with odds ratios or rate ratios (RRs) and 95% CIs calculated. Following stratified PS matching, 1,338 patients were included in both cohorts. At 6 months, the adjusted average number of claims per person for any acute medication was significantly lower in the erenumab cohort (1.13 vs 1.29 in the onabotulinumtoxinA cohort; RR = 0.88; 95% CI = 0.80-0.96; = 0.0069), although the difference in the number of claims for triptans and barbiturates was statistically nonsignificant. The adjusted average number of all-cause and migraine-specific visits per person to health care providers was generally lower in the erenumab cohort compared with the onabotulinumtoxinA cohort. Patients in the erenumab cohort had a significantly lower number of composite events (0.44 vs 0.69 in the onabotulinumtoxinA cohort; RR = 0.63; 95% CI = 0.56-0.71; < 0.0001). Similarly, the adjusted proportion of patients with any of the 3 composite events was lower in the erenumab cohort (31.7% vs 44.3% in the onabotulinumtoxinA cohort; OR = 0.59; 95% CI = 0.49-0.70; < 0.0001). In this retrospective claims analysis study, erenumab significantly reduced acute medication usage (opioids and nonsteroidal anti-inflammatory drugs; any acute medication when analyzed together) and HCRU to a greater extent than onabotulinumtoxinA. This study was supported by Novartis Pharma AG. Novartis employees contributed to the study design, analysis of the data, and the decision to publish the results. Fang, Abdrabboh, Glassberg, Vo, and Ferraris are employed by Novartis. Zhou and Shen are employed by KMK Consulting, Inc., which received funding from Novartis to conduct the study. Tepper reports grants from Allergan, Amgen, ElectroCore, Eli Lilly, Lundbeck, Neurolief, Novartis, Satsuma, and Zosano, outside the submitted work; personal fees from Dartmouth-Hitchcock Medical Center, American Headache Society, Thomas Jefferson University, Aeon, Align Strategies, Allergan/AbbVie, Alphasights, Amgen, Aperture Venture Partners, Aralez Pharmaceuticals Canada, Axsome Therapeutics, Becker Pharmaceutical Consulting, BioDelivery Sciences International, Biohaven, ClearView Healthcare Partners, CoolTech, CRG, Currax, Decision Resources, DeepBench, DRG, Eli Lilly, Equinox, ExpertConnect, GLG, Guidepoint Global Healthcare Consultancy Group, Health Science Communications, HMP Communications, Impel, InteractiveForums, M3 Global Research, Magellan Rx Management, Medicxi, Navigant Consulting, Neurorelief, Nordic BioTech, Novartis, Pulmatrix, Reckner Healthcare, Relevale, SAI MedPartners, Satsuma, Slingshot Insights, Spherix Global Insights, Sudler and Hennessey, Synapse Medical Communications, System Analytic, Teva, Theranica, Thought Leader Select, Trinity Partners, XOC, Zosano, Krog and Partners, and Lundbeck, outside the submitted work; and CME honoraria from American Academy of Neurology, American Headache Society, Cleveland Clinic Foundation, Diamond Headache Clinic, Elsevier, Forefront Collaborative, Hamilton General Hospital, Ontario, Canada, Headache Cooperative of New England, Henry Ford Hospital, Detroit, Inova, Medical Learning Institute PeerView, Medical Education Speakers Network, Miller Medical Communications, North American Center for CME, Physicians' Education Resource, Rockpointe, ScientiaCME, WebMD/Medscape. The abstract and poster of these results were presented at The Migraine Trust Virtual Symposium (MTIS), October 3-9, 2020.
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http://dx.doi.org/10.18553/jmcp.2021.21060DOI Listing
May 2021

Long Noncoding RNA LINC01518 Modulates Proliferation and Migration in TGF-β1-Treated Human Tenon Capsule Fibroblast Cells Through the Regulation of hsa-miR-216b-5p.

Neuromolecular Med 2021 May 15. Epub 2021 May 15.

Center of Myopia, Affiliated Hospital of Inner Mongolia Medical University, 1 Tongdao North St., Hohhot, 010050, Inner Mongolia, China.

In this study, we investigated the expression and functions of long noncoding RNAs (LncRNAs) of LINC01518 in an in vitro model of TGF-β1-treated human Tenon capsule fibroblast (HTF) cells. qRT-PCR was used to examine LINC01518 expression in in situ human glaucoma tissues, and in vitro HTF cells treated with TGF-β1. Lentivirus-mediated LINC01518 knockdown was performed in HTF cells to investigate its effect on TGF-β1-induced cell proliferation, migration and autophagy signaling pathway. The potential ceRNA candidate of LINC01518, hsa-miR-216b-5p, was probed by dual-luciferase assay and qRT-PCR. Hsa-miR-216b-5p was also knocked down in LINC01518-downregulated HTF cells to investigate the function of this lncRNA-miRNA epigenetic axis in TGF-β1-treated HTF cells. LINC01518 was upregulated in human glaucoma tissues and cultured HTF cells. LINC01518 downregulation significantly suppressed TGF-β1-induced cell proliferation, migration and autophagy signaling pathway in HTF cells. Hsa-miR-216b-5p was confirmed to be a ceRNA target of LINC01518. Knocking down hsa-miR-216b-5p reversed the suppressing effects of LINC01518 downregulation in TGF-β1-treated HTF cells. Our study demonstrated that LINC01518 is a functional factor in regulating proliferation and migration in TGF-β1-treated HTF cells, and hsa-miR-216b -5p may also be involved. Targeting the epigenetic axis of LINC01518/hsa-miR-216b-5p may provide new insight into the pathological development of human glaucoma.
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http://dx.doi.org/10.1007/s12017-021-08662-2DOI Listing
May 2021

Utility of Volumetric Metabolic Parameters on Preoperative FDG PET/CT for Predicting Tumor Lymphovascular Invasion in Non-Small Cell Lung Cancer.

AJR Am J Roentgenol 2021 May 12. Epub 2021 May 12.

Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, Hubei Province, China.

Lymphovascular invasion (LVI) is an adverse prognostic indicator in non-small cell lung cancer (NSCLC) and serves as an indication for postoperative adjuvant chemotherapy recommendation after resection. To assess the utility of clinicopathologic factors and volumetric metabolic parameters from preoperative FDG PET/CT in predicting primary tumor LVI in NSCLC. This retrospective study included 161 patients (mean age, 61.8±8.1 years; 111 men, 50 women) with surgically-confirmed NSCLC who underwent preoperative FDG PET/CT between January 2018 and November 2020. Two nuclear medicine physicians used software to place automated volumes of interest delineating each tumor to record metabolic indices (SUVmax, SUVmean, and metabolictumor volume [MTV]), which in turn were used to calculate total lesion glycolysis (TLG). Measurements were first performed independently to determine interobserver agreement using intraclass correlation coefficients (ICCs) and then repeated in consensus. Associations of clinicopathologic and metabolic parameters with tumor LVI status were assessed using t test, Mann-Whitney U test, and chi-squared test. Diagnostic performance was assessed using ROC analysis. Multivariable logistic regression analysis was performed to identify independent predictors of tumor LVI. A total of 23.6% (38/161) of patients had LVI. Interobserver agreement was ICC=1.000 for SUVmax, ICC=0.997 for SUVmean, and 0.999 for MTV. Tumors with LVI, compared with tumors without LVI, exhibited higher SUVmax (15.4±5.9 vs 11.7±7.5, p=.006), SUVmean (6.0±1.6 vs 5.1±2.0, p=.009), MTV (median 15.8 cm3 vs 5.5 cm3, p<.001), and TLG (median 88.8 vs 24.5, p<.001). Among the metabolic parameters, AUC was highest for MTV (0.704), with optimal MTV cutoff of 6.4 cm3 yielding sensitivity 92.1% (35/38), specificity 56.1% (69/123), PPV 39.3% (35/89), and NPV 95.8% (69/72) for LVI. Independent predictors (p<.05) of LVI were MTV (≥6.4 cm3, odds ratio [OR]=6.5), N1 (OR=6.4) or N2 (OR=4.0) disease, and T2 disease (OR=3.6). These factors combined achieved AUC of 0.854 for LVI. The volumetric metabolic parameter MTV from preoperative FDG PET/CT is an independent predictor of tumor LVI in NSCLC. Further studies are warranted to assess the potential role of preoperative prediction of LVI using FDG PET/CT to help guide clinical decision making in NSCLC.
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http://dx.doi.org/10.2214/AJR.21.25814DOI Listing
May 2021

Pen-2 Negatively Regulates the Differentiation of Oligodendrocyte Precursor Cells into Astrocytes in the Central Nervous System.

J Neurosci 2021 Jun 10;41(23):4976-4990. Epub 2021 May 10.

State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, 210061, China

Mutations on γ-secretase subunits are associated with neurologic diseases. Whereas the role of γ-secretase in neurogenesis has been intensively studied, little is known about its role in astrogliogenesis. Recent evidence has demonstrated that astrocytes can be generated from oligodendrocyte precursor cells (OPCs). However, it is not well understood what mechanism may control OPCs to differentiate into astrocytes. To address the above questions, we generated two independent lines of oligodendrocyte lineage-specific presenilin enhancer 2 () conditional KO mice. Both male and female mice were used. Here we demonstrate that conditional inactivation of Pen-2 mediated by or causes enhanced generation of astrocytes. Lineage-tracing experiments indicate that abnormally generated astrocytes are derived from Cre-expressing OPCs in the CNS in conditional KO mice. Mechanistic analysis reveals that deletion of Pen-2 inhibits the Notch signaling to upregulate signal transducer and activator of transcription 3, which triggers activation of GFAP to promote astrocyte differentiation. Together, these novel findings indicate that Pen-2 regulates the specification of astrocytes from OPCs through the signal transducer and activator of transcription 3 signaling. Astrocytes and oligodendrocyte (OLs) play critical roles in the brain. Recent evidence has demonstrated that astrocytes can be generated from OL precursor cells (OPCs). However, it remains poorly understood what mechanism governs the differentiation of OPCs into astrocytes. In this study, we took advantage of OL lineage cells specific presenilin enhancer 2 (Pen-2) conditional KO mice. We show that deletion of Pen-2 leads to dramatically enhanced astrocyte differentiation from OPCs in the CNS. Mechanistic analysis reveals that deletion of Pen-2 inhibits Hes1 and activates signal transducer and activator of transcription 3 to trigger GFAP activation which promotes astrocyte differentiation. Overall, this study identifies a novel function of Pen-2 in astrogliogenesis from OPCs.
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http://dx.doi.org/10.1523/JNEUROSCI.2455-19.2021DOI Listing
June 2021

Short-Term High-Intensity Interval Exercise Promotes Motor Cortex Plasticity and Executive Function in Sedentary Females.

Front Hum Neurosci 2021 23;15:620958. Epub 2021 Apr 23.

Guangdong Provincial Key Laboratory of Sports and Health Promotion, Scientific Research Center, Guangzhou Sport University, Guangzhou, China.

Previous research has demonstrated that regular exercise modulates motor cortical plasticity and cognitive function, but the influence of short-term high-intensity interval training (HIIT) remains unclear. In the present study, the effect of short-term HIIT on neuroplasticity and executive function was assessed in 32 sedentary females. Half of the participants undertook 2 weeks of HIIT. Paired-pulse transcranial magnetic stimulation (ppTMS) was used to measure motor cortical plasticity via short intracortical inhibition (SICI) and intracortical facilitation (ICF). We further adapted the Stroop task using functional near-infrared spectroscopy (fNIRS) to evaluate executive function in the participants. The results indicated that, compared with the control group, the HIIT group exhibited decreased ICF. In the Stroop task, the HIIT group displayed greater activation in the left dorsolateral prefrontal cortex (DLPFC) and left orbitofrontal cortex (OFC) even though no significant difference in task performance was observed. These findings indicate that short-term HIIT may modulate motor cortical plasticity and executive function at the neural level.
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http://dx.doi.org/10.3389/fnhum.2021.620958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102987PMC
April 2021

Superelastic Polyimide Nanofiber-Based Aerogels Modified with Silicone Nanofilaments for Ultrafast Oil/Water Separation.

ACS Appl Mater Interfaces 2021 May 27;13(17):20489-20500. Epub 2021 Apr 27.

Key Laboratory of Eco-Textiles (Ministry of Education), Nonwoven Technology Laboratory, Jiangnan University, Wuxi 214122, China.

Nanofiber membranes via electrospinning with layered structures are frequently used for oil/water separation, thanks to their unique properties. However, challenges that involve nanofibrous membranes still remain, such as high energy consumption and unfavorable transport properties because of the densely compact structure. In this study, superelastic and robust nanofiber-based aerogels (NFAs) with a three-dimensional (3D) structure as well as tunable porosity were prepared using polyimide (PI) nanofibers via a freeze-drying process followed by the solvent-vapor treatment. The porous NFAs were further modified using trichloromethylsilane (TCMS) to generate silicone nanofilaments (SiNFs) on the surface of the PI nanofibers, which could enhance the hydrophobicity (water contact angle 151.7°) of the NFAs. The corresponding superhydrophobic NFAs exhibited ultralow density (<10.0 mg m), high porosity (>99.0%), and rapid recovery under 80% compression strain. SiNFs-coated NFAs (SiNFs/NFAs) could also collect a wide range of oily solvents with high absorption capacities up to 159 times to their own weight. Moreover, surfactant-stabilized water-in-oil emulsions could also be efficiently separated (up to 100%) under the driving force of gravity, making it a promising energy-efficient technology. Additionally, SiNFs/NFAs maintained high separation efficiency throughout five separation-recovery cycles, indicating the potential of SiNFs/NFAs in the field of oil/water separation, sewage treatment, as well as oily fume purification.
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http://dx.doi.org/10.1021/acsami.1c01136DOI Listing
May 2021

Circ_0004104 knockdown alleviates oxidized low-density lipoprotein-induced dysfunction in vascular endothelial cells through targeting miR-328-3p/TRIM14 axis in atherosclerosis.

BMC Cardiovasc Disord 2021 Apr 23;21(1):207. Epub 2021 Apr 23.

Department of Cardiology, The Puren Hospital, No. 218, Changqing First Road, Jianghan District, Wuhan, 430081, Hubei, China.

Background: Circular RNAs have shown important regulatory roles in cardiovascular diseases, containing atherosclerosis (AS). We intended to explore the role of circ_0004104 in AS using oxidized low-density lipoprotein (ox-LDL)-induced vascular endothelial cells and its associated mechanism.

Methods: Real-time quantitative polymerase chain reaction and Western blot assay were conducted to analyze RNA levels and protein levels, respectively. Cell viability, apoptosis, angiogenic ability and inflammatory response were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay, flow cytometry, capillary-like network formation assay and enzyme-linked immunosorbent assay, respectively. Cell oxidative stress was assessed using commercial kits. Dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA-pull down assay were performed to verify the intermolecular interaction.

Results: ox-LDL exposure up-regulated the level of circ_0004104 in HUVECs. ox-LDL exposure suppressed cell viability and angiogenic ability whereas promoted the apoptosis, inflammation and oxidative stress of HUVECs partly through up-regulating circ_0004104. MicroRNA-328-3p (miR-328-3p) was confirmed as a target of circ_0004104. MiR-328-3p interference largely reversed circ_0004104 silencing-mediated effects in HUVECs upon ox-LDL exposure. MiR-328-3p interacted with the 3' untranslated region of tripartite motif 14, and circ_0004104 positively regulated TRIM14 expression by sponging miR-328-3p. TRIM14 overexpression largely overturned miR-328-3p accumulation-induced influences in HUVECs upon ox-LDL exposure.

Conclusion: Circ_0004104 knockdown attenuated ox-LDL-induced dysfunction in HUVECs via miR-328-3p-mediated regulation of TRIM14.
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http://dx.doi.org/10.1186/s12872-021-02012-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066471PMC
April 2021

Nonsynchronous Model Reduction for Uncertain 2-D Markov Jump Systems.

IEEE Trans Cybern 2021 Apr 20;PP. Epub 2021 Apr 20.

Mode information is of great significance when investigating the Markov jump systems (MJSs). However, it is common in practical scenarios that the mode information is not completely accessible, which probably induces nonsynchronization problems. Taking this into consideration, in this article, we study nonsynchronous H∞ model order reduction for 2-D MJSs with model uncertainty. The considered 2-D system and reduced-order model are characterized by the Roesser model. The nonsynchronization phenomenon between the original system and the reduced-order model is dealt with under the framework of the hidden Markov model. By appropriately selecting the Lyapunov function, the asymptotic mean-square stability and the H∞ performance of the error system are analyzed, and sufficient conditions are proposed. Based on this, an efficient design method for nonsynchronous model order reduction is further proposed with the help of a projection lemma. Finally, the correctness and effectiveness of the designed reduced-order model are verified through some simulations.
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http://dx.doi.org/10.1109/TCYB.2021.3069784DOI Listing
April 2021

Impact of erenumab on acute medication usage and health care resource utilization among migraine patients: a US claims database study.

J Headache Pain 2021 Apr 19;22(1):27. Epub 2021 Apr 19.

Novartis Pharma AG, CH-4002, Basel, Switzerland.

Background: Migraine is one of the leading causes of disability worldwide. Erenumab is a fully human monoclonal antibody that targets the calcitonin gene-related peptide (CGRP) receptor. This study aimed to evaluate real-world evidence on the impact of erenumab on acute medication usage and health care resource utilization (HCRU) among migraine patients.

Methods: This retrospective effectiveness study utilized the US Optum's de-identified Clinformatics® Data Mart database to identify migraine patients initiating erenumab between May 1, 2018 and September 30, 2019. Patients had to be at least 18 years old, with a minimum of three doses for erenumab in the 6-month post-index period and continuous medical/pharmacy coverage in the 12-month pre- and 6-month post-index period. The date of the first claim for erenumab served as the index date. Use of acute medications overall and at different drug class level, and HCRU were compared during the 6-month pre- vs. post-index period. Impact of erenumab on a composite endpoint of three possible events: 1) outpatient visit with a diagnosis of migraine and an associated acute medication claim within 7 days of the visit, 2) hospital admission with a primary diagnosis for migraine, or 3) emergency room visit with a primary diagnosis for migraine (any events that occurred ≤3 days apart were counted only once) was also evaluated.

Results: The analysis included 3171 identified patients. At 6 months, following initiation of erenumab, acute medication use including the number of types of acute medication, number of claims of each medication and % of patients who received acute medication, and HCRU were significantly decreased. For the composite outcome, the mean number of events decreased from 1.03 to 0.77 (rate ratio: 0.75; 95% CI: 0.71 to 0.79; P < 0.0001). A decrease in the proportion of patients with any of the three events was also observed (52.7% vs. 39.5%, P < 0.0001).

Conclusion: In this retrospective analysis, erenumab was associated with significantly reduced acute medication use and HCRU in a real-world setting, hence significantly reducing the burden of the disease. A composite endpoint could be used as a proxy to evaluate the burden of migraine attacks; however, further research is needed.
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http://dx.doi.org/10.1186/s10194-021-01238-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054394PMC
April 2021

Risk Factors Associated With Abnormal Urinalysis in Children.

Front Pediatr 2021 25;9:649068. Epub 2021 Mar 25.

Department of Biostatistics, Peking University First Hospital, Beijing, China.

Targeted urinalysis has been suggested to improve screening efficiency in adults. However, there is no well-defined target population in children yet, with limited information on the risk factors for urinalysis abnormalities. Children from infants to 17 years old were randomly selected. Dipstick urinalysis was initially performed. Among those who were abnormal, a repeat dipstick or dipstick with microscopic urinalysis was performed for confirmation. In total, 70,822 children were included, with 37,866 boys and 32,956 girls. Prevalence of abnormal urinalysis was 4.3%. Age was significantly associated with abnormal urinalysis, with the highest prevalence among 12-14-year-olds. Girls were 2.0 times more likely to exhibit abnormalities. Compared with children whose guardians had a college degree or higher, those whose guardians had a high school degree or lower had a higher likelihood of abnormalities. Geographic location was also associated with abnormal results. Girls, children aged 12-14 years old, and children whose guardians had a low educational level and children in certain geographic locations were significantly associated with abnormal urinalysis. Identification of children at high risk would contribute to targeted urinalysis screening.
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http://dx.doi.org/10.3389/fped.2021.649068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044805PMC
March 2021

Circular RNA-HIPK3 regulates human pulmonary artery endothelial cells function and vessel growth by regulating microRNA-328-3p/STAT3 axis.

Pulm Circ 2021 Apr-Jun;11(2):20458940211000234. Epub 2021 Mar 29.

Department of Neonatology, The Children's Hospital of Fuzhou, Fuzhou, People's Republic of China.

The proliferation and migration of pulmonary artery endothelial cells are the pathological basis of pulmonary vascular remodeling with pulmonary hypertension. Recent studies have shown that circular RNA (circRNA) regulates biological processes in various vascular diseases, including pulmonary arterial hypertension. It has been reported that circRNA regulates the vascular endothelial cells' function. Therefore, circRNA may have crucial roles in human pulmonary artery endothelial cells (hPAECs) proliferation, migration, and tube formation in pulmonary arterial hypertension. In this study, we aimed to discover the role and mechanism of circular RNA HIPK3 (circHIPK3) in the proliferation and migration of pulmonary hypertension hPAECs. First, we used platelet-derived growth factor-stimulated hPAECs as a cellular model of pulmonary arterial hypertension. The results showed that platelet-derived growth factor promoted hPAECs proliferation, migration, and tube formation. Notably, platelet-derived growth factor upregulated the expression of circHIPK3 in hPAECs and regulated their proliferation, migration, and angiogenesis. Mechanistically, we confirmed miR-328-3p was copiously pulled down by circHIPK3 in hPAECs. Luciferase reporter and RNA immunoprecipitation assays further indicated the cytoplasmic interactions between circHIPK3 and miR-328-3p. Subsequently, we found that circHIPK3 might increase the expression of STAT3 by sponging miR-328-3p. Collectively, our results demonstrated that the circHIPK3-miR-328-3p-STAT3 axis contributed to the pathogenesis of pulmonary arterial hypertension by stimulating hPAECs proliferation, migration, and angiogenesis. The circHIPK3 has an accelerated role in pulmonary arterial hypertension development, implicating the potential values of circHIPK3 in pulmonary arterial hypertension therapy.
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http://dx.doi.org/10.1177/20458940211000234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010839PMC
March 2021

Subsoiling increases aggregate-associated organic carbon, dry matter, and maize yield on the North China Plain.

PeerJ 2021 24;9:e11099. Epub 2021 Mar 24.

College of Agronomy, Shandong Agricultural University, Tai'an, Shandong Province, P.R. China.

Background: Soil degradation is one of the main problems in agricultural production and leads to decreases in soil quality and productivity. Improper farming practices speed this process and are therefore not conducive to food security. The North China Plain (NCP) is a key agricultural area that greatly influences food security in China. To explore the effects of different tillage measures on aggregate-associated organic carbon (AOC), the accumulation and transport of dry matter, and maize yield, and to identify the most suitable tillage method for use on the NCP, a field experiment was conducted at Shandong Agricultural University from 2016-2017 using plots that have been farmed using conservation tillage since 2002.

Methods: In this study, Zhengdan 958 summer maize was used as the test material and undisturbed soil and plant samples were obtained under four tillage methods-no-tillage (NT, tillage depth: 0 cm); rotary tillage (RT, tillage depth: 10 cm); conventional tillage (CT, tillage depth: 20 cm); subsoiling (SS, tillage depth: 40 cm)-which were used to determine the AOC and dry matter contents, as well as the yields of two summer maize growing seasons. Each sample was replicated three times and the AOC content was determined via potassium dichromate oxidation colorimetry. Potassium dichromate oxidized organic carbon in organic matter was employed to reduce hexadecent chromium into green trivalent chromium. Colorimetry was then used to determine the amount of reduced trivalent chromium and calculate the organic matter content.

Results: The resulting data were statistically analyzed and the results showed that, compared with CT, the AOC contents with NT and SS increased by 5.65% and 9.73%, respectively, while that with RT decreased by 0.12%. Conventional tillage resulted in the highest mean dry matter weight when the maize reached maturity, which was 19.19%, 9.83%, and 3.38% higher than those achieved using NT, RT, and SS, respectively. No significant difference was found between CT and SS treatments, both of which tended to increase the accumulation of dry matter as well as its contribution of assimilates to grain yield post-anthesis. Compared with CT, the mean yield increased at a rate of 0.18% with SS, while yields declined at rates of 17.17% and 11.15 with NT and RT, respectively. The yield with NT was the lowest, though the harvest indices with NT and SS were higher than those with RT and CT. Overall, SS increased the accumulation of dry matter and its contribution of assimilates to grain yields post-anthesis, as well as the AOC content and yields, making it the ideal tillage method for the NCP.
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http://dx.doi.org/10.7717/peerj.11099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000453PMC
March 2021

Maintaining Inducibility of Dermal Follicle Cells on Silk Fibroin/Sodium Alginate Scaffold for Enhanced Hair Follicle Regeneration.

Biology (Basel) 2021 Mar 26;10(4). Epub 2021 Mar 26.

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, China.

The extracellular matrix (ECM) is important for maintaining cell phenotype and promoting cell proliferation and differentiation. In order to better solve the problem of skin appendage regeneration, a combination of mechanical/enzymatic digestion methods was used to self-extract dermal papilla cells (DPCs), which were seeded on silk fibroin/sodium alginate scaffolds as seed cells to evaluate the possibility of skin regeneration/regeneration of accessory organs. Scanning electron microscopy (SEM) graphs showed that the interconnected pores inside the scaffold had a pore diameter in the range of 153-311 μm and a porosity of 41-82%. Immunofluorescence (IF) staining and cell morphological staining proved that the extracted cells were DPCs. The results of a Cell Counting Kit-8 (CCK-8) and Calcein-AM/PI live-dead cell staining showed that the DPCs grew well in the composite scaffold extract. Normal cell morphology and characteristics of aggregation growth were maintained during the 3-day culture, which showed that the silk fibroin/sodium alginate (SF/SA) composite scaffold had good cell-compatibility. Hematoxylin-eosin (H&E) staining of tissue sections further proved that the cells adhered closely and aggregated to the pore wall of the scaffold, and retained the ability to induce differentiation of hair follicles. All these results indicate that, compared with a pure scaffold, the composite scaffold promotes the adhesion and growth of DPCs. We transplanted the SF/SA scaffolds into the back wounds of SD rats, and evaluated the damage model constructed in vivo. The results showed that the scaffold inoculated with DPCs could accelerate the repair of the skin and promote the regeneration of the hair follicle structure.
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http://dx.doi.org/10.3390/biology10040269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066588PMC
March 2021

Molecular Behavior of HMGB1 in the Cochlea Following Noise Exposure and .

Front Cell Dev Biol 2021 25;9:642946. Epub 2021 Feb 25.

Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Noise-induced hearing loss (NIHL) is characterized by cellular damage to the inner ear, which is exacerbated by inflammation. High-mobility group box 1 (HMGB1), a representative damage-associated molecular pattern (DAMP), acts as a mediator of inflammation or an intercellular messenger according to its cellular localization. Blocking or regulating HMGB1 offers an attractive approach in ameliorating NIHL. However, the precise therapeutic intervention must be based on a deeper understanding of its dynamic molecular distribution and function in cochlear pathogenesis after acoustic trauma. Here, we have presented the spatiotemporal dynamics of the expression of HMGB1, exhibiting distribution variability in specific cochlear regions and cells following noise exposure. After gene manipulation, we further investigated the characteristics of cellular HMGB1 in HEI-OC1 cells. The higher cell viability observed in the HMGB1 knocked-down group after stimulation with HO indicated the possible negative effect of HMGB1 on cellular lifespan. In conclusion, this study demonstrated that HMGB1 is involved in NIHL pathogenesis and its molecular biology has essential and subtle influences, preserving a translational potential for pharmacological intervention.
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http://dx.doi.org/10.3389/fcell.2021.642946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959764PMC
February 2021

Deletion of in Cerebellar Granule Cells Impairs Synaptic Development and Motor Performance.

Front Cell Dev Biol 2020 25;8:627146. Epub 2021 Feb 25.

Department of Physiology, School of Medicine, Zhejiang University, Hangzhou, China.

The cerebellum is conceptualized as a processor of complex movements. Many diseases with gene-targeted mutations, including Fahr's disease associated with the loss-of-function mutation of meningioma expressed antigen 6 (), exhibit cerebellar malformations, and abnormal motor behaviors. We previously reported that the defects in cerebellar development and motor performance of Nestin-Cre; mice are severer than those of Purkinje cell-targeted pCP2-Cre; mice, suggesting that Mea6 acts on other types of cerebellar cells. Hence, we investigated the function of Mea6 in cerebellar granule cells. We found that mutant mice with the specific deletion of in granule cells displayed abnormal posture, balance, and motor learning, as indicated in footprint, head inclination, balanced beam, and rotarod tests. We further showed that Math1-Cre; mice exhibited disrupted migration of granule cell progenitors and damaged parallel fiber-Purkinje cell synapses, which may be related to impaired intracellular transport of vesicular glutamate transporter 1 and brain-derived neurotrophic factor. The present findings extend our previous work and may help to better understand the pathogenesis of Fahr's disease.
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http://dx.doi.org/10.3389/fcell.2020.627146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946997PMC
February 2021

Impact of glycemic control on the association of endothelial dysfunction and coronary artery disease in patients with type 2 diabetes mellitus.

Cardiovasc Diabetol 2021 03 13;20(1):64. Epub 2021 Mar 13.

Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai, 200025, People's Republic of China.

Background: We investigated whether glycemic control affects the relation between endothelial dysfunction and coronary artery disease in patients with type 2 diabetes mellitus (T2DM).

Methods: In 102 type 2 diabetic patients with stable angina, endothelial function was evaluated using brachial artery flow-mediated dilation (FMD) with high-resolution ultrasound, and significant stenosis of major epicardial coronary arteries (≥ 50% diameter narrowing) and degree of coronary atherosclerosis (Gensini score and SYNTAX score) were determined. The status of glycemic control was assessed by blood concentration of glycated hemoglobin (HbA1c).

Results: The prevalence of significant coronary artery stenosis (67.9% vs. 37.0%, P = 0.002) and degree of coronary atherosclerosis (Gensini score: 48.99 ± 48.88 vs. 15.07 ± 21.03, P < 0.001; SYNTAX score: 15.88 ± 16.36 vs. 7.28 ± 10.54, P = 0.003) were higher and FMD was lower (6.03 ± 2.08% vs. 6.94 ± 2.20%, P = 0.036) in diabetic patients with poor glycemic control (HbA1c ≥ 7.0%; n = 56) compared to those with good glycemic control (HbA1c < 7.0%; n = 46). Multivariate regression analysis revealed that tertile of FMD was an independent determinant of presence of significant coronary artery stenosis (OR = 0.227 95% CI 0.056-0.915, P = 0.037), Gensini score (β =  - 0.470, P < 0.001) and SYNTAX score (β =  - 0.349, P = 0.004) in diabetic patients with poor glycemic control but not for those with good glycemic control (P > 0.05).

Conclusion: Poor glycemic control negatively influences the association of endothelial dysfunction and coronary artery disease in T2DM patients.
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http://dx.doi.org/10.1186/s12933-021-01257-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956110PMC
March 2021

Long non-coding RNA-based glycolysis-targeted cancer therapy: feasibility, progression and limitations.

Mol Biol Rep 2021 Mar 11;48(3):2713-2727. Epub 2021 Mar 11.

Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157, 5th West Road, Xi'an, 710004, Shaanxi, China.

Metabolism reprogramming is one of the hallmarks of cancer cells, especially glucose metabolism, to promote their proliferation, metastasis and drug resistance. Cancer cells tend to depend on glycolysis for glucose utilization rather than oxidative phosphorylation, which is called the Warburg effect. Genome instability of oncogenes and tumor-inhibiting factors is the culprits for this anomalous glycolytic fueling, which results in dysregulating metabolism-related enzymes and metabolic signaling pathways. It has been extensively demonstrated that protein-coding genes are involved in this process; therefore, glycolysis-targeted therapy has been widely used in anti-tumor combined therapy via small molecular inhibitors of key enzymes and regulatory molecular. The long non-coding RNA, which is a large class of regulatory RNA with longer than 200 nucleotides, is the novel and significant regulator of various biological processes, including metabolic reprogramming. RNA interference and synthetic antisense oligonucleotide for RNA reduction have developed rapidly these years, which presents potent anti-tumor effects both in vitro and in vivo. However, lncRNA-based glycolysis-targeted cancer therapy, as the highly specific and less toxic approach, is still under the preclinical phase. In this review, we highlight the role of lncRNA in glucose metabolism and dissect the feasibility and limitations of this clinical development, which may provide potential targets for cancer therapy.
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http://dx.doi.org/10.1007/s11033-021-06247-7DOI Listing
March 2021

MKL1 cooperates with p38MAPK to promote vascular senescence, inflammation, and abdominal aortic aneurysm.

Redox Biol 2021 May 20;41:101903. Epub 2021 Feb 20.

Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, USA; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA, USA. Electronic address:

Abdominal aortic aneurysm (AAA) is a catastrophic disease with little effective therapy. Myocardin related transcription factor A (MRTFA, MKL1) is a multifaceted transcription factor, regulating diverse biological processes. However, a detailed understanding of the mechanistic role of MKL1 in AAA has yet to be elucidated. In this study, we showed induced MKL1 expression in thoracic and abdominal aneurysmal tissues, respectively in both mice and humans. MKL1 global knockout mice displayed reduced AAA formation and aortic rupture compared with wild-type mice. Both gene deletion and pharmacological inhibition of MKL1 markedly protected mice from aortic dissection, an early event in Angiotensin II (Ang II)-induced AAA formation. Loss of MKL1 was accompanied by reduced senescence/proinflammation in the vessel wall and cultured vascular smooth muscle cells (VSMCs). Mechanistically, a deficiency in MKL1 abolished AAA-induced p38 mitogen activated protein kinase (p38MAPK) activity. Similar to MKL1, loss of MAPK14 (p38α), the dominant isoform of p38MAPK family in VSMCs suppressed Ang II-induced AAA formation, vascular inflammation, and senescence marker expression. These results reveal a molecular pathway of AAA formation involving MKL1/p38MAPK stimulation and a VSMC senescent/proinflammatory phenotype. These data support targeting MKL1/p38MAPK pathway as a potential effective treatment for AAA.
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http://dx.doi.org/10.1016/j.redox.2021.101903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937568PMC
May 2021

Erratum: Overcoming erlotinib resistance in EGFR mutation-positive lung adenocarcinomas through repression of phosphoglycerate dehydrogenase: Erratum.

Theranostics 2021 9;11(8):3963. Epub 2021 Feb 9.

Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

[This corrects the article DOI: 10.7150/thno.23177.].
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http://dx.doi.org/10.7150/thno.58558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914359PMC
February 2021

A rare complex rearrangement in the β-globin gene cluster causing a novel homozygous γ( γδβ) -thalassemia.

Am J Hematol 2021 06 22;96(6):E189-E193. Epub 2021 Mar 22.

Department of Obstetrics/Gynecology, Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1002/ajh.26148DOI Listing
June 2021

RefineDNet: A Weakly Supervised Refinement Framework for Single Image Dehazing.

IEEE Trans Image Process 2021 9;30:3391-3404. Epub 2021 Mar 9.

Haze-free images are the prerequisites of many vision systems and algorithms, and thus single image dehazing is of paramount importance in computer vision. In this field, prior-based methods have achieved initial success. However, they often introduce annoying artifacts to outputs because their priors can hardly fit all situations. By contrast, learning-based methods can generate more natural results. Nonetheless, due to the lack of paired foggy and clear outdoor images of the same scenes as training samples, their haze removal abilities are limited. In this work, we attempt to merge the merits of prior-based and learning-based approaches by dividing the dehazing task into two sub-tasks, i.e., visibility restoration and realness improvement. Specifically, we propose a two-stage weakly supervised dehazing framework, RefineDNet. In the first stage, RefineDNet adopts the dark channel prior to restore visibility. Then, in the second stage, it refines preliminary dehazing results of the first stage to improve realness via adversarial learning with unpaired foggy and clear images. To get more qualified results, we also propose an effective perceptual fusion strategy to blend different dehazing outputs. Extensive experiments corroborate that RefineDNet with the perceptual fusion has an outstanding haze removal capability and can also produce visually pleasing results. Even implemented with basic backbone networks, RefineDNet can outperform supervised dehazing approaches as well as other state-of-the-art methods on indoor and outdoor datasets. To make our results reproducible, relevant code and data are available at https://github.com/xiaofeng94/RefineDNet-for-dehazing.
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http://dx.doi.org/10.1109/TIP.2021.3060873DOI Listing
March 2021