Publications by authors named "Lixin Guo"

115 Publications

Genome‑wide profiling of DNA methylation and gene expression unravel the epigenetic landscape in diabetes-related hypothyroidism.

Clin Epigenetics 2021 Jun 6;13(1):123. Epub 2021 Jun 6.

Department of Endocrinology, The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No.1 DaHua Road, Dong Dan, Beijing, 100730, People's Republic of China.

Background: Type 2 diabetes mellitus (T2DM) and hypothyroidism are two common endocrine diseases and the phenomenon that the prevalence of diabetes-related hypothyroidism shows a significant upward trend deserves further attention, but the specific pathogenesis is not yet clear. The study aimed to explore the molecular mechanisms on DNA methylation regulating gene expression and participating in diabetes-related hypothyroidism through genome-wide DNA methylation and RNA sequencing.

Results: The prevalence of hypothyroidism in T2DM patients was significantly higher than that in patients without T2DM (P = 0.018). Meanwhile, high TSH and low T3 and T4 levels were detected in diabetic mice. Low T3 and T4 levels were detected in Nthy-ori3-1 cells incubated in high-glucose medium. Differentially expressed genes (DEGs) and differentially methylated regions (DMRs) were detected by RNA sequencing and reduced representation bisulfite sequencing in Nthy-ori3-1 cells cultured in high-glucose and normal medium. Functional enrichment analyses reveled that DMRs and DEGs were related to significant pathways including Ras, Wnt and MAPK pathways.

Conclusions: We observed the potential connection between T2DM and hypothyroidism. This study was the first one carrying out DNA methylation and gene expression profiles to explore epigenetic modification in diabetes-related hypothyroidism, which provided information for the detailed study of the molecular mechanism in diabetes-related hypothyroidism.
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http://dx.doi.org/10.1186/s13148-021-01109-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182906PMC
June 2021

Early neurovascular changes in the retina in preclinical diabetic retinopathy and its relation with blood glucose.

BMC Ophthalmol 2021 May 17;21(1):220. Epub 2021 May 17.

Department of Endocrinology, Beijing Hospital, Nations Center of Gerontology, Beijing, China.

Background: To investigate the changes in retinal nerve fiber layer thickness and macular blood flow density during the preclinical stage of diabetic retinopathy and their relationship with blood glucose.

Methods: In this cross-sectional study, 97 diabetic patients (total of 188 eyes; 144 eyes in no diabetic retinopathy group, 44 eyes in mild diabetic non-proliferative retinopathy group) and 35 healthy people (70 eyes) were enrolled, All the subjects were divided into different groups based on their HbA1c levels, and they underwent optical coherence tomography angiography. We compared the optical coherence tomography angiography parameters and retinal nerve fiber layer thickness among the different glucose groups.

Results: The parafoveal vessel density and the temporal retinal nerve fiber layer thickness were lower (p < 0.05) in the diabetic group than in the normal group. The diabetic group showed a higher acircularity index than the normal group. The normal group had the highest vessel density and the lowest acircularity index, followed by the no-diabetic retinopathy group and the mild non-proliferative retinopathy group, (p < 0.001). Foveal vascular density and parafoveal vessel density decreased with an increase in HbA1c. There was a negative correlation between parafoveal vessel density in the deep retinal vascular layer and fasting blood glucose (p < 0.01). The temporal retinal nerve fiber layer thickness decreased across the HbA1c level groups, and was positively correlated with the parafoveal vessel density in the superficial retinal vascular layer (p < 0.05).

Conclusions: This study shows that retinal microvasculopathy and neuropathy can be present in the absence of retinopathy. The vessel density of the deep retinal vascular layer was negatively correlated with fasting blood glucose, and the temporal retinal nerve fiber layer thickness was positively correlated with the vessel density of the superficial retinal vascular layer. These indicators are helpful for endocrinologists and ophthalmologists in detecting early diabetic retinal pathological lesions.
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http://dx.doi.org/10.1186/s12886-021-01975-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130389PMC
May 2021

Statistical model for the weak turbulence-induced attenuation and crosstalk in free space communication systems with orbital angular momentum.

Opt Express 2021 Apr;29(8):12644-12662

A novel statistical model connected with turbulence strength is proposed to describe the attenuation and crosstalk in a vortex-based multi-channel free space optical (FSO) communication system. In this model, self-channel fading and interference between different orbital angular momentum (OAM) modes are characterized by the mixture exponential-generalized-gamma (EGG) distribution, and the analytical relations between turbulence strength and the distribution function's parameters are expressed by piecewise functions. The problems of obtaining parameters of this model are converted into optimization problems, and the algorithms based on the trust trigon algorithm are proposed to achieve more optimized parameters. This model is confirmed to have a good fit with the emulated data of OAM attenuation and crosstalk calculated by the square of the scalar product between the fields of two OAM modes. Furthermore, the application of the statistical model to the OAM-multiplexing FSO system with quadrature-phase-shift-keying modulation is presented, in which the theoretical average bit-error rate results match well with Monte Carlo simulation. This model can be used for FSO system design with OAM for continuous weak turbulence condition.
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http://dx.doi.org/10.1364/OE.420011DOI Listing
April 2021

Association of thyroid disorders with gestational diabetes mellitus: a meta-analysis.

Endocrine 2021 May 13. Epub 2021 May 13.

Department of Endocrinology, The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, PR China.

Purpose: The current meta-analysis aimed to evaluate the association of thyroid dysfunction and autoimmunity with gestational diabetes mellitus (GDM).

Methods: A comprehensive search from PubMed, Embase, MEDLINE, and Cochrane databases until November 2020 was conducted. Fixed-effect model was used to combine the results when I was <50%. Random-effect model was used to summarize the results when I was >50%.

Results: A total of 44 studies were included in the meta-analysis. Low FT4 levels were closely related with GDM in the first and second trimesters of gestation. Hypothyroxinemia (OR: 1.45; 95% CI: 1.25, 1.68; P < 0.00001), overt (OR: 1.80; 95% CI: 1.73, 1.86; P < 0.00001), and subclinical (OR: 1.54; 95% CI: 1.03, 2.30; P = 0.03) hypothyroidism, overt hyperthyroidism (OR: 1.49; 95% CI: 1.09, 2.04; P = 0.01), and positive thyroid antibodies (OR: 1.49; 95% CI: 1.07, 2.07; P < 0.00001) were observed significantly associated with the risk of GDM. Pregnant women with subclinical hyperthyroidism were less likely to develop GDM (OR: 0.62; 95% CI: 0.39, 0.97; P = 0.04).

Conclusions: Thyroid dysfunction and positive thyroid antibodies were associated with the risk of GDM. Our findings suggest that pregnant women with these thyroid diseases may be offered screening for GDM comprehensively.
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http://dx.doi.org/10.1007/s12020-021-02712-2DOI Listing
May 2021

Time-restricted feeding restored insulin-growth hormone balance and improved substrate and energy metabolism in MC4RKO obese mice.

Neuroendocrinology 2021 Mar 18. Epub 2021 Mar 18.

Background Dysregulation of metabolic regulatory hormones often occurs during the progress of obesity. Key regulatory hormone Insulin-GH balance has recently been proposed to maintain metabolism profiles. Time-restricted feeding (TRF) is an effective strategy against obesity without detailed research on pulsatile GH releasing patterns. Methods TRF was performed in an over-eating MC4RKO obese mouse model using normal food. Body weight and food intake were measured. Series of blood samples were collected for 6 h pulsatile GH profile, glucose tolerance test and insulin tolerance test at 5, 8, and 9 weeks of TRF, respectively. Indirect calorimetric recordings were performed by Phenomaster system at 6 weeks for 1 week and body composition was measured by Nuclear magnetic resonance spectroscopy (NMR). Substrate and energy metabolism related gene expression were measured in terminal liver and subcutaneous white adipose tissues. Results TRF increased pulsatile GH secretion in dark phase and suppressed hyperinsulinemia in MC4RKO obese mice to reach a reduced insulin/GH ratio. This was accompanied by the improvement in insulin sensitivity, metabolic flexibility, glucose tolerance and decreased glucose fluctuation, together with appropriate modification of gene expression involved in substrate metabolism and adipose tissue browning. NMR measurement showed that TRF decreased fat mass but increased lean mass. Indirect calorimeter recording indicated that TRF decreased the respiratory exchange ratio (RER) reflecting consumption of more fatty acid in energy production in light phase and increased the oxygen consumption during activities in dark phase. Conclusions TRF effectively decreases hyperinsulinemia and restores pulsatile GH secretion in the overeating obese mice with significant improvement in substrate and energy metabolism and body composition without reducing total caloric intake.
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http://dx.doi.org/10.1159/000515960DOI Listing
March 2021

Iron Deficiency, a Risk Factor of Thyroid Disorders in Reproductive-Age and Pregnant Women: A Systematic Review and Meta-Analysis.

Front Endocrinol (Lausanne) 2021 25;12:629831. Epub 2021 Feb 25.

Department of Endocrinology, Beijing Hospital, The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.

Background: Iron deficiency (ID) is concerned as the most common nutritional deficiency worldwide. The effects of ID on thyroid function and autoimmunity in pregnant women and reproductive-age women are controversial. The aim of the current study was to summarize the evidences and evaluate the relationship between ID and thyroid disorders.

Methods: In this systematic review and meta-analysis, studies published on the Cochrane, Embase, Medline, and PubMed databases by October 2020 were searched. A total of 636 studies which discussed the correlation between ID and thyroid disorders were eligible in the initial search. Pooled mean differences (MD) and 95% confidence intervals (CI) were calculated for the assessment of thyrotropin (TSH) and free thyroxine (FT4) levels. Combined odd ratios (OR) and 95% CI were calculated for the assessment of the prevalence of overt and subclinical hypothyroidism, positive thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb).

Results: For women of reproductive age, ID could significantly increase the risk of positive TPOAb (OR: 1.89; 95% CI: 1.17, 3.06: = 0.01) and both positive TPOAb and TgAb (OR: 1.48; 95% CI: 1.03, 2.11: = 0.03). The meta-analysis of pregnant women showed that pregnant women with ID had increased serum TSH levels (MD: 0.12; 95% CI: 0.07, 0.17; P < 0.00001) and decreased FT4 levels (MD: -0.73; 95% CI: -1.04, -0.41; P < 0.00001). Meanwhile, the prevalence of overt (OR: 1.60; 95% CI: 1.17, 2.19; P = 0.004) and subclinical (OR: 1.37; 95% CI: 1.13, 1.66; P = 0.001) hypothyroidism in pregnant women with ID was significantly increased.

Conclusions: ID may adversely affect thyroid function and autoimmunity of pregnant and reproductive-age women and it is very necessary for monitoring iron nutritional status and early treatment of ID for them.
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http://dx.doi.org/10.3389/fendo.2021.629831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947868PMC
February 2021

Composite cardiovascular risk and BMI affected comparative profiles of BIAsp 30 + metformin vs BIAsp 30 monotherapy: a MERIT post-hoc analysis.

Sci Rep 2021 Feb 18;11(1):4131. Epub 2021 Feb 18.

Department of Endocrinology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1, Dahua Road, Dongcheng District, Beijing, 100730, China.

We assessed whether comparative efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) plus metformin versus BIAsp 30 monotherapy differed for patients with type 2 diabetes mellitus (T2DM) inadequately controlled with oral antidiabetic drugs with different cardiovascular risk scores and different body mass indexes (BMI) by performing a post hoc analysis of the randomized controlled MERIT study. In the MERIT study, eligible patients were randomized 1:1 to receive BIAsp 30 plus metformin or BIAsp 30 for 16 weeks. Patients in the 2 treatment groups were classified into "low" and "high" risk subgroups based on their GloboRisk scores and into "BMI ≤ 26 kg/m"and "BMI > 26 kg/m" subgroups. Primary efficacy endpoint was between-treatments comparison of HbA1c changes from baseline for these 2 sets of subgroups. Between-treatments comparisons of secondary efficacy and safety endpoints were also performed. We found that BIAsp 30 plus metformin led to significantly higher percentage of high-risk patients achieving HbA1c target < 7% than BIAsp 30 monotherapy, with an overall comparable safety profile for high-risk patients. Meanwhile, for patients with BMI ≤ 26 kg/m, compared with BIAsp 30 monotherapy, BIAsp 30 plus metformin led to significantly higher percentages of patients achieving HbA1c target (47.83% vs 28.17%, P = 0.0165) and composite target of HbA1c < 7% without hypoglycemia or weight gain (20.29% vs 6.85%, P = 0.0187) and have a slightly better safety profile. In conclusion, for T2DM patients at high CV risk or with BMI ≤ 26 kg/m, BIAsp 30 plus metformin was preferable to BIAsp 30 monotherapy.
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http://dx.doi.org/10.1038/s41598-021-83410-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893025PMC
February 2021

A novel GLP-1 and FGF21 dual agonist has therapeutic potential for diabetes and non-alcoholic steatohepatitis.

EBioMedicine 2021 Jan 7;63:103202. Epub 2021 Jan 7.

Department of Endocrinology, National Center of Gerontology, Beijing Hospital, Beijing, China. Electronic address:

Background: Fibroblast growth factor 21 (FGF21) has become a promising therapeutic target for metabolic diseases such as type 2 diabetes (T2D), obesity and non-alcoholic steatohepatitis. However, the clinical application of natural FGF21 molecule is limited because of its instability in vitro and short half-life in vivo. To improve FGF21's therapeutic property, we screened high receptor binding FGF21 analogs and made FGF21-Fc-GLP-1 dual-targeted constructs to investigate their activity in a number of experiments .

Methods: Utilizing phage display high-throughput screening we identified mutations that could improve β-Klotho binding property of FGF21. IgG4 Fc was fused to FGF21 variants to extend the in vivo half-life. We further explored the potential synergistic actions of FGF21 with the incretin glucagon-like peptide-1 (GLP-1) by generating GLP-1-Fc-FGF21 dual agonists.

Findings: Two Fc-FGF21 variants showed enhanced β-Klotho binding affinity in vitro as well as improved glucose lowering effect in vivo. One of the dual agonists, GLP-1-Fc-FGF21 D1, provided potent and sustained glucose lowering effect in diabetic mice models. It also demonstrated superior weight loss effect to GLP-1 or FGF21 alone. Moreover, GLP-1-Fc-FGF21 D1 exhibited strong anti-NASH effect in the high-fat diet-induced ob/ob model as it improved liver function, serum and hepatic lipid profile and reduced NAFLD activity score with an efficacy superior to either FGF21 or GLP-1 analogs alone.

Interpretation: This novel GLP-1/FGF21 dual agonist is worth clinical development for the treatment of T2D, obesity and NASH.

Funding: HEC Pharm R&D Co., Ltd, National natural science fund of China.
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http://dx.doi.org/10.1016/j.ebiom.2020.103202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806870PMC
January 2021

Application of new international classification of adult-onset diabetes in Chinese inpatients with diabetes mellitus.

Diabetes Metab Res Rev 2020 Dec 4. Epub 2020 Dec 4.

Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.

Background: To determine whether the new international cluster-based classification method can be applied to Chinese inpatients with diabetes mellitus (DM).

Methods: Adult patients with DM hospitalized in our tertiary care centre from January 2017 to December 2018 were included in the study. K-means cluster analysis was done in clusters based on glutamic acid decarboxylase antibodies, body mass index, glycosylated haemoglobin, homeostasis model-assessed beta cell function, insulin resistance index, and age at diagnosis of DM. Chi-square test was used to analyse inter-subgroup differences in DM-related complications and family history of DM. p < 0.05 was considered significant.

Results: A total of 1152 inpatients with DM were included in the study. Five subgroups were obtained by cluster analysis with highest proportion of population in mild obesity-related DM subgroup (34.55%), followed by mild age-related DM (21.55%), severe insulin deficiency DM (20.51%), severe insulin resistance DM (19.02%), and severe autoimmune DM subgroup (4.36%). The prevalence of diabetic retinopathy, diabetic peripheral vascular disease, diabetic ketosis, coronary heart disease, hypertension, and family history of DM differed significantly among the subgroups (p < 0.05 for all).

Conclusions: This cluster-based classification could be applied to hospitalized adult patients with DM in China. It might help in strategizing for DM patients, and hence, improve management of DM in these patients.
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http://dx.doi.org/10.1002/dmrr.3427DOI Listing
December 2020

Metabolic and Nutritional Characteristics in Middle-Aged and Elderly Sarcopenia Patients with Type 2 Diabetes.

J Diabetes Res 2020 4;2020:6973469. Epub 2020 Nov 4.

Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, 100730, China.

Sarcopenia is considered to be a new complication of type 2 diabetes (T2DM) leading to increased risk of adverse outcome. We performed a survey to evaluate glucose metabolism and nutritional status in sarcopenia patients with T2DM. Diabetic participants aged ≥50 years were grouped into a probable sarcopenia group with low muscle strength ( = 405) and a nonsarcopenia group with normal muscle strength ( = 720) according to the revised recommendations from EWGSOP2 (2018). Compared to the controls, the probable sarcopenia participants were older and had lower waist-to-hip ratio and BMI, longer diabetes duration, higher fasting plasma glucose level and glycosylated hemoglobin (HbA1c), decreased estimated glomerular filtration rate and lower bone mineral content, lower fatless upper arm circumference, lower appendicular skeletal muscle mass index (ASMI), and muscle quality in both genders. Multivariable logistic regression analysis showed increased age, male, low BMI, and increased HbA1c, combined with diabetic nephropathy and decreased serum albumin levels, were risk factors associated with low muscle strength in diabetes patients. In conclusion, diabetic patients with sarcopenia had worse glucose metabolism and nutritional status, decreased renal function and reduced muscle quality ,and muscle mass with a greater likelihood of osteoporosis, who need an overall health management to improve outcomes. This clinical trial registration is registered with the Chinese Clinical Trial Registry, ChiCTR-EOC-15006901.
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http://dx.doi.org/10.1155/2020/6973469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661113PMC
November 2020

Suppression of Insulin Secretion in the Treatment of Obesity: A Systematic Review and Meta-Analysis.

Obesity (Silver Spring) 2020 11;28(11):2098-2106

School of Biomedical Sciences, University of Queensland, St Lucia, Brisbane, Queensland, Australia.

Objective: This proof-of-concept study aimed to evaluate the efficacy and safety of suppression of insulin secretion in the treatment of obesity.

Methods: A search of PubMed, Embase, and Cochrane databases was performed to identify randomized controlled trials (up to January 1, 2020) that used drugs that directly suppress insulin secretion (diazoxide or octreotide) in the treatment of obesity. The extracted data were analyzed using random-effects meta-analysis.

Results: A total of seven randomized controlled trials were included, with four using diazoxide and three using octreotide to suppress insulin secretion. Suppression of insulin secretion significantly reduced fasting insulin level (mean difference: -3.94 mIU/L; 95% CI: -7.40 to -0.47) but slightly increased fasting blood glucose level (mean difference: 0.48 mmol/L; 95% CI: 0.24 to 0.72). Following the suppression of insulin secretion, significant reductions in body weight (mean difference: -3.19 kg; 95% CI: -5.71 to -0.66), BMI (mean difference: -1.65 kg/m ; 95% CI: -2.41 to -0.90), and fat mass (mean difference: -5.92 kg; 95% CI: -8.28 to -3.56) were observed compared with placebo in the pooled data. No significant difference in fat-free mass was observed (mean difference: 0.56 kg; 95% CI: -0.40 to 1.52).

Conclusions: Results suggest that suppression of insulin secretion may lead to reduced body weight and fat mass with slightly increased blood glucose in individuals with obesity.
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http://dx.doi.org/10.1002/oby.22955DOI Listing
November 2020

Glucose-lowering pharmacotherapies in Chinese adults with type 2 diabetes and cardiovascular disease or chronic kidney disease. An expert consensus reported by the Chinese Diabetes Society and the Chinese Society of Endocrinology.

Diabetes Metab Res Rev 2021 May 23;37(4):e3416. Epub 2020 Nov 23.

Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, China.

Patients with type 2 diabetes mellitus (T2DM) are at risk of developing atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD), which are important causes of disabling and death in patients with T2DM. For the prevention and management of ASCVD or CKD, cardiovascular risk factors should be systematically evaluated, and ASCVD and CKD should be screened in patients with T2DM. In this consensus, we recommended that metformin should be used as the first-line therapy for patients with T2DM and ASCVD or very high cardiovascular risk, heart failure (HF) or CKD, and should be retained in the treatment regimen unless contraindicated or not tolerated. In patients with T2DM and established ASCVD or very high cardiovascular risk, addition of a glucagon-like peptide 1 receptor agonist (GLP-1RA) or sodium-glucose cotransporter type 2 (SGLT2) inhibitor with proven cardiovascular benefits should be considered independent of individualised glycated haemoglobin (HbA ) targets. In patients with T2DM and HF, an SGLT2 inhibitor should be preferably added regardless of HbA levels. In patients with T2DM and CKD, SGLT2 inhibitors should be preferred for the combination therapy independent of individualised HbA targets, and GLP-1RAs with proven renal benefits would be alternative if SGLT2 inhibitors are contraindicated. Moreover, the prevention of hypoglycaemia and management of multiple risk factors by comprehensive regimen, including lifestyle intervention, antihypertensive therapies, lipid-lowering treatment and antiplatelet therapies, should be kept in mind in treating patients with T2DM and ASCVD, HF or CKD.
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http://dx.doi.org/10.1002/dmrr.3416DOI Listing
May 2021

LncRNA PART1 Exerts Tumor-Suppressive Functions in Tongue Squamous Cell Carcinoma via miR-503-5p.

Onco Targets Ther 2020 7;13:9977-9989. Epub 2020 Oct 7.

Department of Scientific Education, Jinan Stomatological Hospital, Jinan, Shandong 250001, People's Republic of China.

Background: Tongue squamous cell carcinoma (TSCC) accounts for one-third of oral cancers. Previous studies had reported that lncRNA/miRNA regulated the biological behaviors of different cancer cells. However, the mechanisms of PART1 in regulating tumorigenesis and TSCC development via targeting miR-503-5p had not been studied.

Methods: The expressions of PART1 and miR-503-5p in tissues and cultured cell lines were detected by qRT-PCR. StarBase 3.0 was used to predict the binding sites of PART1, then dual-luciferase assay and RNA pull-down assay were executed to confirm whether miR-503-5p was a target of PART1. TSCC cells were co-transfected with PART1-overexpressed plasmid or miR-503-5p mimics in vitro, and the transfection efficiency was evaluated through qRT-PCR. Western blot was performed to assess the expressions of EMT-related proteins. CCK-8 and clone formation assays were conducted to detect cell proliferation, TUNEL assay was used to detect apoptosis, and transwell assay was executed to test migration and invasion.

Results: The low PART1 expression and high miR-503-5p expression were found in TSCC tissues and cell lines (CAL-27 and SCC9). PART1 expression was positively correlated with patients' prognosis. The targeting and binding relationship between PART1 and miR-503-5p was confirmed, and overexpressed PART1 diminished the expression of miR-503-5p as well. Moreover, PART1 facilitated apoptosis, inhibited proliferation, invasion and migration of TSCC cells, and these influences were impeded by miR-503-5p overexpression.

Conclusion: LncRNA PART1 played a cancer-suppressing role in TSCC by targeting miR-503-5p, which provided a potential target for TSCC treatment.
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http://dx.doi.org/10.2147/OTT.S264410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548330PMC
October 2020

Parallel Monte Carlo simulation algorithm for the spectral reflectance and transmittance of the wind-generated bubble layers in the upper ocean using CUDA.

Authors:
Yu Yang Lixin Guo

Opt Express 2020 Oct;28(22):33538-33555

The parallel Monte Carlo software CUDAMCML used in the bio-optics field was developed by Erik Alerstam et al. (J. Biomed. Opt., 13, 060504, 2008) based on the Compute Unified Device Architecture (CUDA) and can simulate light transport in multilayered media. In the present study, CUDAMCML is extended to form the new program CUDAMCML-OCEAN using the average sampling method. This new program can handle multiple types of particle seawater containing elements such as colored dissolved organic matter (CDOM) and bubbles. The accuracy and speedup of the new program are analyzed. The results show that when the parameters are set appropriately, the speedup of CUDAMCML-OCEAN is more than 200 times compared with serial code. And the accuracies of the spectral reflectance and transmittance all reached a satisfactory level for different wind speeds and chlorophyll concentrations.
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http://dx.doi.org/10.1364/OE.406262DOI Listing
October 2020

Aerosol scattering of vortex beams transmission in hazy atmosphere.

Opt Express 2020 Sep;28(19):28072-28084

Mie theory is widely used for the simulation and characterization of optical interaction with scattering media, such atmospheric pollutants. The complex refractive index of particle plays an important role in determining the scattering and absorption of light. Complex optical fields, such as vortex beams, will interact with scattering particulates differently to plane wave or Gaussian optical fields. By considering the three typical aerosol particles compositions that lead to haze in the atmosphere, distinctive scattering dynamic were identified for vortex beams as compared to Gaussian beams. Using parameters similar to real world atmospheric conditions, a new aerosol particle model is proposed to efficiently and concisely describe the aerosol scattering. Numerical simulations indicate unique signatures in the scattering dynamics of the vortex beams that can indicate particles composition and also suggest that potentially there is higher optical transmission of vortex beams propagating in certain hazy environments.
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http://dx.doi.org/10.1364/OE.401293DOI Listing
September 2020

Oxycodone protects cardiomyocytes from ischemia-reperfusion-induced apoptosis via PI3K/Akt pathway.

Pharmazie 2020 09;75(9):430-435

Department of Cardiovascular Surgery, Third Hospital of Xingtai (Xingtai Cardiovascular Hospital), Xintai, China;, Email:

Ischemia/reperfusion (I/R) cause secondary myocardial damage following a blood reflow after myocardial infarction. This study aimed to explore oxycodone as a myocardial protector after an I/R injury in rats. Oxycodone reduced myocardial infarction volume, an I/R-induced apoptosis of the cardiomyocytes, the serum levels of CK-MB and LDH. The ejection fraction and fraction shortening in the I/R rats also increased. From the molecular mechanism, it was evident that oxycodone not only decreased the expression levels of Bax, active-caspase 3 protein but also increased the expression levels of Bcl2, p-PI3K, and p-Akt protein in heart tissue of the I/R rats. , oxycodone induced anti-H9c2 cell apoptosis after hypoxia/reoxygenation (H/R). However, its ability to act as a myocardial protector deteriorated in the presence of a PI3K/Akt pathway inhibitor.
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http://dx.doi.org/10.1691/ph.2020.0497DOI Listing
September 2020

Identification of prognostic factors for intrahepatic cholangiocarcinoma using long non-coding RNAs-associated ceRNA network.

Cancer Cell Int 2020 16;20:315. Epub 2020 Jul 16.

Department of Hematology and Oncology, the Second Hospital of Jilin University, No. 218, Ziqiang Street, Changchun, 130022 Jilin People's Republic of China.

Background: Accumulating amount of evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor pathogenesis. However, the roles of long non coding RNAs (lncRNAs) in the lncRNA-related ceRNA network of intrahepatic cholangiocarcinoma (ICC) still remain enigmatic. The current study aims to identify prognostic factors in the lncRNA-related ceRNA network of ICC.

Methods: The transcriptome sequencing data of lncRNAs, messenger RNA (mRNA) and microRNA (miR) were downloaded from the SRA and TCGA databases. Differentially expressed lncRNAs (DElncRNAs), DEmiRs and DEmRNAs were identified and adopted to construct an lncRNA-miR-mRNA ceRNA network. ICC-associated DEmRNAs were adopted to construct the protein-protein interaction (PPI) network. The expression of the top 6 genes in the hub module was validated with mRNA transcriptome sequencing data and ICC-related gene expression dataset GSE45001, followed by GO and KEGG pathway enrichment analysis. The relationship between the hub gene-associated ceRNA network and the overall survival of patients with ICC was predicted by conducting a Kaplan-Meier survival analysis.

Results: Sixty co-expressed DEmRNAs were identified in the ceRNA network. The top 6 hub genes consisted of downregulated FOS, IGF2, FOXO1 and NTF3, upregulated IGF1R, and insignificantly downregulated HGF in ICC tissues, when compared to that of normal adjacent tissues, followed by the successful construction of lncRNA-miR-hub network consisting of 86 ceRNA modules. MME-AS1 and hsa-miR-182 were associated with overall survival in ICC patients. FOS, IGF1R, IGF2, FOXO1, and NTF3 might target "TGF-β signaling pathway", "the hedgehog signaling pathway", "retinol metabolism", or "type II diabetes mellitus" pathways respectively.

Conclusion: These results indicate that FOS, IGF1R, IGF2, FOXO1, and NTF3 were useful prognostic factors in determining the prognosis of patients with ICC.
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http://dx.doi.org/10.1186/s12935-020-01388-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364620PMC
July 2020

Evaluation of Characteristics of Gastrointestinal Adverse Events with Once-Weekly Dulaglutide Treatment in Chinese Patients with Type 2 Diabetes: A Post Hoc Pooled Analysis of Two Randomized Trials.

Diabetes Ther 2020 Aug 4;11(8):1821-1833. Epub 2020 Jul 4.

Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, 410011, Hunan, China.

Introduction: Gastrointestinal (GI) events are a common side effect of glucagon-like peptide 1 (GLP-1) receptor agonists (RA) class. This post hoc analysis assessed the characteristics of GI adverse events in Chinese patients with type 2 diabetes (T2D) who were treated with once-weekly dulaglutide from two randomized clinical trials.

Methods: Chinese patients with T2D, treated with once-weekly dulaglutide (1.5 mg and 0.75 mg) from two phase III multicenter trials (AWARD-CHN1 and AWARD-CHN2) were included. Descriptive statistics were used to present the data. The characteristics (incidence, severity, onset, duration, and time of occurrence) of GI adverse events reported through 26 weeks in a Chinese subpopulation from the two trials were investigated.

Results: A total of 787 Chinese patients with T2D were included in this analysis. Up to week 26, 225 patients (28.6%) reported at least one GI treatment-emergent adverse event (TEAE). The most frequently reported GI TEAEs were diarrhea (13.1%), nausea (6.6%), abdominal distension (6.4%), and vomiting (3.0%), with most being categorized as mild to moderate in severity in proportions of 92%, 88%, 94%, and 83%, respectively. A total of 12 patients (1.5%) discontinued the dulaglutide treatment as a result of GI TEAEs. The median duration of the first reported GI TEAEs was 4.0, 5.0, 12.5, and 4.0 days for diarrhea, nausea, abdominal distension, and vomiting, respectively. The incidence of GI TEAEs was more frequent during the first 2 weeks of dulaglutide treatment; however, the incidence declined rapidly after 2 weeks and remained low until week 26.

Conclusions: Most of the GI TEAEs associated with once-weekly dulaglutide (1.5 mg and 0.75 mg) were mild to moderate in severity. The incidence of GI TEAEs was more pronounced during the first 2 weeks of dulaglutide treatment but declined rapidly as treatment continued, and was low at week 26, indicating that dulaglutide was well tolerated in Chinese patients with T2D.

Trial Registration: NCT01648582 and NCT01644500.
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http://dx.doi.org/10.1007/s13300-020-00869-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376772PMC
August 2020

Insulin delivery with a needle-free insulin injector versus a conventional insulin pen in Chinese patients with type 2 diabetes mellitus: A 16-week, multicenter, randomized clinical trial (the FREE study).

EClinicalMedicine 2020 Jun 4;23:100368. Epub 2020 Jun 4.

Department of Endocrinology, the First Affiliated Hospital of China Medical University, Shenyang, China.

Background: Insulin therapy is poorly accepted by patients with type 2 diabetes mellitus (T2DM). A needle-free insulin injector has been developed for patients who fear injections or are reluctant to initiate insulin therapy when it is clearly indicated. The objective of this trial was to evaluate the glucose-lowering effect, tolerability, patient satisfaction and compliance with insulin treatment via a needle-free insulin injector (NFII) compared with insulin treatment via a conventional insulin pen (CIP) in patients with T2DM.

Methods: A total of 427 patients with T2DM were enrolled in a prospective, multicenter, randomized, open-label study, and were randomly assigned 1:1 to receive 16 weeks' treatment with basal insulin or premixed insulin administered either by a NFII or CIP.

Trial Registration: ClinicalTrials.gov (NCT03243903).

Findings: In the 412 patients who completed the study, the adjusted mean reduction of HbA1c from baseline at week 16 in the NFII group was 0.55% (95% CI -0.71, -0.39), which was non-inferior and statistically superior to the HbA1c reduction in the CIP group (0.26%, 95% CI -0.42, -0.11). Patients in the NFII group showed significantly higher treatment satisfaction scores than those in the CIP group (mean scores, 8.17 ± 1.78 vs. 7.21 ± 2.22, respectively; <0.0001). The occurrence of hypoglycemia was similar in the two groups, and the NFII group showed reduced incidences of skin scratches, indurations and lower VAS pain scores.

Interpretation: Insulin therapy through needle-free injector showed a non-inferior glycemic-lowering effect and a significantly enhanced level of patient satisfaction with insulin treatment compared with conventional insulin therapy through needle injections. In addition, the needle-free injector also had a better safety profile.

Funding: This study were funded by Beijing QS Medical Technology Co., Ltd, as well as The Major Chronic Non-communicable Disease Prevention and Control Research.
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http://dx.doi.org/10.1016/j.eclinm.2020.100368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283138PMC
June 2020

Evaluation of the safety of sodium-glucose co-transporter-2 inhibitors for treating patients with type 1 diabetes.

Diabetes Obes Metab 2020 10 22;22(10):1767-1776. Epub 2020 Jun 22.

Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.

Aim: To conduct an overall safety assessment of sodium-glucose co-transporter-2 (SGLT-2) inhibitors used for the treatment of patients with type 1 diabetes (T1D), including ketoacidosis, genital infection, volume depletion, liver and kidney injury events, cardiovascular events, diarrhea and severe hypoglycaemia.

Materials And Methods: We searched three databases (Pubmed, Embase and the Cochrane Library) for randomized controlled trials that treated T1D by using SGLT-2 inhibitors from 2000 to 5 March 2020.

Results: Of the 1653 articles identified that fit our search criteria, 22 studies included qualitative-based results, eight of which were randomized clinical trials that included quantitative-based results. Compared with the control group, the SGLT-2 inhibitors treatment group was found to have had an increased incidence of ketoacidosis (P < .00001, OR 4.34, 95% CI [2.37, 7.96], I = 18%), events leading to discontinuation (P < .0001, OR 1.76, 95% CI [1.34, 2.31], I = 0%), genital infection (P < .00001, OR 3.64, 95% CI [2.82, 4.70], I = 0%), volume depletion (P = .006, OR 2.10, 95% CI [1.23, 3.59], I = 4%) and diarrhoea (P = .008, OR 1.64, 95% CI [1.14, 2.36], I = 0%). However, according to subgroup analysis, the risk of diarrhoea was dose-related. The incidence of urinary tract infection, cardiovascular events, renal events, liver injury and fracture was not significantly different for the treatment group compared with the control group.

Conclusions: Despite showing some promise as a treatment approach, the application of SGLT-2 inhibitors for patients with T1D should be considered with caution.
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http://dx.doi.org/10.1111/dom.14092DOI Listing
October 2020

ABER performance investigation of LDPC-coded multi-hop parallel underwater wireless optical communication system: publisher's note.

Appl Opt 2020 May;59(14):4566

This publisher's note corrects several equations and a sentence in Appl. Opt.59, 1353 (2020)APOPAI0003-693510.1364/AO.59.001353.
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http://dx.doi.org/10.1364/AO.396514DOI Listing
May 2020

ABER performance investigation of LDPC-coded multi-hop parallel underwater wireless optical communication system.

Appl Opt 2020 Feb;59(5):1353-1362

The average bit error rate (ABER) performance of a low-density parity-check (LDPC)-coded multi-hop parallel underwater wireless optical communication (UWOC) system is investigated with the combined effects of absorption, scattering, the misalignment characterized by the beam spread function, and the ocean turbulence-induced fading modeled by log-normal distribution. With the max-min criterion as the best path selection scheme, the cumulative distribution function for identically and independently distributed and non-identically and independently distributed links are derived, respectively. Then, the analytical ABER expressions of binary phase shift keying and multiple phase shift keying subcarrier intensity modulation schemes are deduced with the help of the Gauss-Laguerre quadrature rule, and they are also confirmed by Monte Carlo simulation. In addition, LDPC codes are applied in the simulation to improve the system performance. The results show that the combined degrading effects are mainly limited by the link length, especially under the coastal ocean condition. And the multi-hop parallel transmission demonstrates good ABER performance and can expand the communication range in ocean. Furthermore, LDPC codes can significantly improve the ABER performance of the UWOC system, and the coding gain is strongly affected by channel conditions and the corresponding parameters of LDPC codes. This work is beneficial for the UWOC system design.
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http://dx.doi.org/10.1364/AO.59.001353DOI Listing
February 2020

Efficacy and safety of generic exenatide injection in Chinese patients with type 2 diabetes: a multicenter, randomized, controlled, non-inferiority trial.

Acta Diabetol 2020 Aug 23;57(8):991-1000. Epub 2020 Mar 23.

Department of Endocrinology and Metabolism, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, People's Republic of China.

Aims: This study aimed to compare the efficacy and safety of generic exenatide with branded exenatide Byetta in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on monotherapy or combination therapy of metformin and insulin secretagogues.

Methods: A multicenter, randomized, controlled, non-inferiority trial was performed. A total of 240 patients with T2DM and glycated hemoglobin (HbA1c) ≥ 7% (53 mmol/mol) to ≤ 9.0% (75 mmol/mol) on monotherapy or combination therapy of metformin and insulin secretagogues for at least 3 months were randomized into generic exenatide or branded exenatide groups with a 1:1 ratio for 16 weeks of treatment. The primary endpoint was the change in HbA1c levels from baseline at week 16, with a non-inferiority margin of - 0.35% (- 3.83 mmol/mol) (lower bound of one-sided 95% confidence interval (CI) > - 0.35% (- 3.83 mmol/mol)). Secondary endpoints included the proportion of participants achieving HbA1c < 7% (53 mmol/mol), the changes in fasting plasma glucose (FPG), 2-h postprandial glucose (2hPG) following a standard meal, 7-point self-monitoring blood glucose (SMBG) profiles, body weight change from baseline at week 16 and the change in HbA1c levels from baseline at week 8. Safety issues were also evaluated.

Results: After 16 weeks of treatment, HbA1c levels decreased significantly from baseline in the two groups, with a reduction of - 1.10% ± 1.31% (- 12.0 mmol/mol ± 14.3 mmol/mol) in the generic exenatide group and - 1.08% ± 1.11% (- 11.8 mmol/mol ± 12.1 mmol/mol) in the branded exenatide group (both P < 0.001). The least-squares mean difference of HbA1c reduction between the two groups was - 0.03% (- 0.33 mmol/mol), with a lower one-sided 95% CI limit of - 0.27% (- 2.95 mmol/mol), which was higher than the prespecified non-inferiority margin of - 0.35% (- 3.83 mmol/mol). Moreover, there were no significant differences in the proportion of participants achieving HbA1c < 7% (53 mmol/mol) and the changes in FPG, 2hPG, 7-point SMBG profiles and body weight at week 16 and the change in HbA1c levels from baseline at week 8 (all P > 0.05) between the two groups. The incidence of adverse events, including the incidence of hypoglycemia (18.3% and 17.5%, respectively), was similar for the generic and branded exenatide groups (P > 0.05).

Conclusions: In patients with T2DM inadequately controlled on monotherapy or combination therapy of metformin and insulin secretagogues, add-on treatment with generic exenatide demonstrated non-inferiority to branded exenatide in terms of improvements in HbA1c after 16 weeks of treatment. Furthermore, the two drugs were also similar for other efficacy endpoints and safety profile. Trial registration Chinese Clinical Trial Registry: ChiCTR-IPR-15006558, Date registered May 27, 2015.
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http://dx.doi.org/10.1007/s00592-020-01510-yDOI Listing
August 2020

Efficacy and Safety of Basal Insulin-Based Treatment Versus Twice-Daily Premixed Insulin After Short-Term Intensive Insulin Therapy in Patients with Type 2 Diabetes Mellitus in China: Study Protocol for a Randomized Controlled Trial (BEYOND V).

Adv Ther 2020 04 4;37(4):1675-1687. Epub 2020 Mar 4.

Endocrinology Department, Beijing Hospital, Beijing, China.

Introduction: Many Chinese patients who are uncontrolled by oral antidiabetic drugs (OADs) receive short-term intensive insulin therapy (IIT) in hospital to rapidly relieve glucose-associated toxicity and to preserve/improve β-cell function. However, evidence for optimizing insulin algorithms for maintenance treatment after IIT is lacking. This study will compare the efficacy and safety of basal insulin-based treatment versus twice-daily premixed insulin in type 2 diabetes mellitus (T2DM) patients after short-term in-hospital IIT.

Methods: This 26-week randomized, multicenter, positive-controlled, open-label, parallel-group study will enroll approximately 400 male and female patients aged 18-70 years with poorly-controlled T2DM (HbA1c > 7.5%) despite treatment with metformin plus at least one other OAD for 8 or more weeks. During a run-in period of 7-10 days, patients will be treated in-hospital with IIT comprising insulin glargine (Lantus) once daily and insulin glulisine (Apidra) three times daily; both regimens will be titrated daily to achieve the glycemic goal. Eligible patients will then be randomized in a 1:1 ratio to insulin glargine plus OADs or twice-daily premixed insulin (NovoLog Mix 70/30) for 24 weeks, with metformin maintained throughout the study in both treatment groups. The primary endpoint is HbA1c change from baseline to week 24. Secondary endpoints include assessment of fasting plasma glucose, total daily insulin dose, hypoglycemia incidence, body weight change, adverse events, and patient satisfaction.

Discussion: Given the current lack of clinical data, this study will provide evidence supporting safe and effective glycemic control using basal insulin glargine-based therapy plus OADs compared with twice-daily premixed insulin in Chinese patients with T2DM after short-term IIT. This will assist physicians by providing a wider choice of treatments.

Trial Registration: ClinicalTrials.gov identifier, NCT03359837 (registered on 2 December 2017).
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http://dx.doi.org/10.1007/s12325-020-01265-6DOI Listing
April 2020

Whole grain food diet slightly reduces cardiovascular risks in obese/overweight adults: a systematic review and meta-analysis.

BMC Cardiovasc Disord 2020 02 18;20(1):82. Epub 2020 Feb 18.

Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Background: The effects of whole grain diet on cardiovascular risks in obese and overweight adults is not well established. Our goal was to conduct a systematic review and meta-analysis on the effect of whole grain diet on cardiovascular risks in obese/overweight adults.

Methods: PubMed, Embase and Cochrane were systematically scanned for randomized controlled trials (RCTs), and studies were selected based on certain inclusion and exclusion criteria. The primary outcome was the effectiveness of whole grain food consumption in reducing body weight. The secondary outcomes were the effect of whole grain food consumption on cardiovascular disease (CVD) risk factors including plasma low-density lipoprotein cholesterol (LDL-C), insulin resistance index, blood pressure, body mass index (BMI), C-reactive protein (CRP), and waist circumference in obese/overweight adults.

Results: Our results showed that whole grain consumption was associated with lower body weight (mean difference (MD) = - 0.5, 95% confidence intervals (CI) [- 0.74, 0.25], I = 35%, P < 0.0001) and lower CRP (MD = -0.36, 95% CI [- 0.54, - 0.18], I = 69%, P < 0.0001), compared with the control group. However, there were no significant differences in LDL-C (MD = -0.08, 95% CI [- 0.16, 0.00], I = 27%, P = 0.05), waist circumference (MD = -0.12, 95% CI [- 0.92, 0.68], I = 44%, P = 0.76), systolic blood pressure (MD = -0.11, 95% CI [- 1.55, 1.33], I = 3%, P = 0.88), diastolic blood pressure (MD = -0.44, 95% CI [- 1.44, 0.57], I = 15%, P = 0.39), and fasting glucose (MD = -0.05, 95% CI [- 0.12, 0.01], I = 31%, P = 0.11) between the two groups.

Conclusion: This study suggests that whole grain food consumption can slightly reduce body weight and CRP in obese/overweight population.
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http://dx.doi.org/10.1186/s12872-020-01337-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027052PMC
February 2020

First-Principles Calculations of the Electronic Structure and Optical Properties of Yttrium-Doped ZnO Monolayer with Vacancy.

Materials (Basel) 2020 Feb 5;13(3). Epub 2020 Feb 5.

School of Information Science & Technology, Northwest University, Xi'an 710127, China.

The electronic structures and optical characteristics of yttrium (Y)-doped ZnO monolayers (MLs) with vacancy (zinc vacancy, oxygen vacancy) were investigated by the first-principles density functional theory. Calculations were performed with the GGA+U (generalized gradient approximation plus U) approach, which can accurately estimate the energy of strong correlation semiconductors. The results show that the formation energy values of Y-doped ZnO MLs with zinc or oxygen vacancy (V, V) are positive, implying that the systems are unstable. The bandgap of Y-V-ZnO was 3.23 eV, whereas that of Y-V-ZnO was 2.24 eV, which are smaller than the bandgaps of pure ZnO ML and Y-doped ZnO MLs with or without V. Impurity levels appeared in the forbidden band of ZnO MLs with Y and vacancy. Furthermore, Y-V-ZnO will result in a red-shift of the absorption edge. Compared with the pure ZnO ML, ZnO MLs with one defect (Y, V or V), and Y-V-ZnO, the absorption coefficient of Y-V-ZnO was significantly enhanced in the visible light region. These findings demonstrate that Y-V-ZnO would have great application potential in photocatalysis.
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http://dx.doi.org/10.3390/ma13030724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040613PMC
February 2020

Functional network analysis of gene-phenotype connectivity based on pioglitazone.

Exp Ther Med 2019 Dec 1;18(6):4790-4798. Epub 2019 Nov 1.

Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Beijing 100010, P.R. China.

Pioglitazone, a type of insulin sensitizer, serves as an effective anti-hyperglycemic drug. The mechanism of action of pioglitazone is through the activation of the peroxisome proliferator-activated receptor (PPAR), which results in enhanced insulin sensitivity of peripheral tissues and the liver, causing a reduction in the production and output of liver sugar. It has been reported that pioglitazone increases the risk of bladder cancer, but the underlying mechanisms have remained elusive. It was hypothesized that modulation of pioglitazone activity may be predicted by systematically analyzing data published on drugs. This hypothesis was tested by querying the Drug-Target Interactome (DTome), a web-based tool that provides open-source data from three databases (DrugBank, PharmGSK and Protein Interaction Network analysis). A total of 4 direct target proteins (DTPs) and further DTP-associated genes were identified for pioglitazone. Subsequently, an enrichment analysis was performed for all DTP-associated genes using Cytoscape software. A total of 12 Kyoto Encyclopedia of Genes and Genomes pathways were identified, including the 'PPAR signaling pathway' as well as 'pathways in cancer' as relevant pathways. Functional network analysis was able to identify direct and indirect target genes of pioglitazone, resulting in a list of possible biological functions based on published databases. Furthermore, Kaplan-Meier analysis indicated that pioglitazone may affect the survival rate of patients with bladder cancer through genetic alterations (missense mutation, truncating mutation, amplification, deep deletion and fusion) of target genes. Therefore, it should be used with caution.
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http://dx.doi.org/10.3892/etm.2019.8162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880387PMC
December 2019

Prevalence and Diagnosis of Diabetic Cardiovascular Autonomic Neuropathy in Beijing, China: A Retrospective Multicenter Clinical Study.

Front Neurosci 2019 25;13:1144. Epub 2019 Oct 25.

Department of Endocrinology, China-Japan Friendship Hospital, Beijing, China.

Cardiovascular autonomic neuropathy (CAN) is a debilitating condition occurring among diabetic patients especially those with long duration of disease. Whereas incidences and treatment of CAN has been well described for Western populations, fewer studies have been conducted among the Chinese. This study, therefore, aimed to assess the prevalence of CAN among sampled Chinese diabetic patients. Accordingly, 2,048 participants with a history of type 1 diabetes mellitus (T1DM, 73) and type 2 diabetes mellitus (T2DM, 1975) were randomly sampled from 13 hospitals. Patients' biodata were recorded, and autonomic nervous system function tests performed to aid in the preliminary diagnosis of CAN. The final CAN diagnosis was based on the Ewing's test in which heart rate variation (HRV) values were evaluated through deep-breathing (DB), lying-to-standing (LS), and Valsalva (V) tests. Systolic blood pressure (SBP) variation values were also evaluated through LS. In the T1DM group, 61.6% patients were diagnosed with CAN and no differences were observed in the baseline and clinical data between this group and those without CAN ( > 0.05). In the T2DM group, 62.6% patients were diagnosed with CAN and statistically significant differences were found between the CAN and non- CAN group with regards to age, duration of diabetes, metformin treatment, retinopathy, and hypertension history ( < 0.05). The most common manifestations of CAN included weakness (28.6%), dizziness (23.4%), frequent urination (19.6%), upper body sweating (18.3%), and nocturia (15.9%). Additionally, duration of disease and age were independent risk factors for CAN in T1DM and T2DM, respectively. On diagnosis, a combination of the V test + LS test provided the highest sensitivity of detecting CAN among T1DM group (sensitivity = 97.6%, AUC = 0.887) while for T2DM category, DB test had the highest sensitivity (83.6%), and maximal AUC (0.856) was found with V test + DB test. The overall prevalence of diabetes with CAN in the study was up to 63%.
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http://dx.doi.org/10.3389/fnins.2019.01144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823192PMC
October 2019

Tetrahydrocurcumin protects against spinal cord injury and inhibits the oxidative stress response by regulating FOXO4 in model rats.

Exp Ther Med 2019 Nov 5;18(5):3681-3687. Epub 2019 Sep 5.

Department of Minimally Invasive Spine Surgery, The 309th Hospital of The People's Liberation Army, Beijing 100091, P.R. China.

It has been reported that tetrahydrocurcumin has hypoglycemic, hypolipidemic, anti-metastasis, anticancer and anti-depressant pharmacological effects, and its antioxidative, hypoglycemic and hypolipidemic properties are better than those of curcumin. The present study assessed whether tetrahydrocurcumin exerts a neuroprotective effect against spinal cord injury (SCI) and investigated the underlying mechanisms. In a rat model of SCI, tetrahydrocurcumin enhanced the average Basso-Beattie-Bresnahan scores, inhibited water accumulation in the spinal cord and decreased inflammatory factors. Furthermore, oxidative stress and apoptosis (caspase-3 activity and B-cell lymphoma 2-associated X protein levels) were also suppressed in SCI rats treated with tetrahydrocurcumin. Tetrahydrocurcumin effectively decreased the gene expression of matrix metalloproteinase-3 and -13, as well as cyclooxygenase-2, promoted the phosphorylation of Akt and enhanced the protein expression of forkhead box (FOX)O4 in SCI rats. The present study delineates that tetrahydrocurcumin protects against SCI and inhibits the oxidative stress response by regulating the FOXO4 in SCI model rats.
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http://dx.doi.org/10.3892/etm.2019.7974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777287PMC
November 2019

Average capacity of a UWOC system with partially coherent Gaussian beams propagating in weak oceanic turbulence.

J Opt Soc Am A Opt Image Sci Vis 2019 Sep;36(9):1463-1474

The average capacity of a single-input single-output (SISO) underwater wireless optical communication (UWOC) system with partially coherent Gaussian beams in a weak oceanic turbulence regime is investigated. An approximate analytical expression of scintillation index is derived mathematically to characterize the impact of oceanic turbulence on the propagation behavior of the partially coherent Gaussian beams. Then, the path loss caused by absorption and scattering in the ocean is numerically simulated with the Monte Carlo method. With consideration for absorption, scattering, and oceanic turbulence, the combined channel fading model is established, and the average capacity of the UWOC system (defined as the maximum mutual information between the input and output) is examined. Results show that the scintillations are reduced by decreases in propagation distance, the dissipation rate of mean-square temperature, and the ratio of the temperature and salinity contributions to the refractive index spectrum. Scintillations are also decreased by increases in source beam width, degree of partial coherence, and the dissipation rate of turbulent kinetic energy per unit mass of fluid. As a result, the average capacity of the UWOC system is enhanced. Moreover, the average capacity of the UWOC system can be promoted with the availability of channel state information at the receiver. This work will benefit the research and development of UWOC systems.
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http://dx.doi.org/10.1364/JOSAA.36.001463DOI Listing
September 2019