Publications by authors named "Yanbing Li"

211 Publications

A Novel Intronic Circular RNA Antagonizes Influenza Virus by Absorbing a microRNA That Degrades CREBBP and Accelerating IFN-β Production.

mBio 2021 Jul 20:e0101721. Epub 2021 Jul 20.

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China.

Virus-host interactions are complicated processes, and multiple cellular proteins promote or inhibit viral replication through different mechanisms. Recent progress has implicated circular RNAs (circRNAs) in cancer biology and progression; however, the role of circRNAs in viral infection remains largely unclear. Here, we detected 11,620 circRNAs in A549 cells and found that 411 of them were differentially expressed in influenza virus-infected A549 cells. We characterized a novel intronic circRNA, AIVR, that was upregulated in influenza virus-infected A549 cells and found that silencing of AIVR significantly promoted influenza virus replication in A549 cells. We further found that AIVR predominantly localizes in the cytoplasm and works as a microRNA (miRNA) sponge. One of the miRNAs absorbed by AIVR binds the mRNA of CREBBP, which is an important component of the large nucleoprotein complex interferon beta (IFN-β) enhanceosome that accelerates IFN-β production. AIVR overexpression significantly increased the mRNA and protein levels of IFN-β in the influenza virus-infected A549 cells. Therefore, the upregulation of AIVR is a cellular antiviral strategy, with AIVR exerting its antiviral effect by absorbing miRNA and promoting the expression of CREBBP to facilitate IFN-β production. Our study provides new insights into the roles of circRNAs in the cellular innate antiviral response. Circular RNAs (circRNAs) are new members of the long noncoding RNA families and have been identified in a variety of organisms, including plants, animals, and humans. Accumulating data indicate that circRNAs perform multiple functions in a variety of cellular processes associated with human diseases, such as Alzheimer's disease and cancer; however, the roles of circRNAs in virus infection have been largely uninvestigated. In this study, we investigated the cellular circRNA response upon influenza virus infection and found that 411 circRNAs were differentially expressed in the virus-infected cells. We identified a novel human intronic circRNA (we named AIVR) that antagonizes influenza virus replication. Upregulated circRNA AIVR absorbs an miRNA that binds the mRNA of CREBBP, leading to an increase in the cellular expression of CREBBP and then accelerating IFN-β production. This study advances the understanding of the roles of circRNAs in the cellular innate antiviral response.
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http://dx.doi.org/10.1128/mBio.01017-21DOI Listing
July 2021

Association Between Prospective Registration and Quality of Systematic Reviews in Type 2 Diabetes Mellitus: A Meta-epidemiological Study.

Front Med (Lausanne) 2021 28;8:639652. Epub 2021 Jun 28.

Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

We sought to investigate the methodological and reporting quality of published systematic reviews describing randomized controlled trials in type 2 diabetes mellitus and analyze their association with status of protocol registration. We searched the PubMed database and identified non-Cochrane systematic reviews, with or without meta-analysis, reporting on type 2 diabetes mellitus and published between 2005 and 2018. We then randomly selected 20% of these reviews in each year, and performed methodological and reporting quality assessment using the Assessment of Multiple Systematic Review 2 (AMSTAR-2) checklist and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. We also conducted regression analyses to explore the association between characteristics of systematic reviews and AMSTAR-2 or PRISMA scores. A total of 238 systematic reviews, including 33 registered and 205 non-registered articles, met the inclusion criteria and were subsequently reviewed. Analysis indicated an increase in both registered rates and quality of systematic reviews in type 2 diabetes mellitus over the recent years. With regards to methodological and reporting quality, we found higher scores in registered, relative to non-registered reviews (AMSTAR-2 mean score: 18.0 vs. 14.5, = 0.000; PRISMA mean score: 20.4 vs. 17.6, = 0.000). AMSTAR-2 and PRISMA scores were associated with registration status, country of the first author, and statistical results, whereas the proportion of discussing publication bias and reporting funding sources were <40% for both registered and non-registered systematic reviews. Methodological and reporting quality of systematic reviews in type 2 diabetes mellitus indicates an improvement in the recent years. However, the overall quality remains low, necessitating further improvement. Future studies are expected to pay more attention to prospective registration, description of publication bias and reporting of funding sources.
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http://dx.doi.org/10.3389/fmed.2021.639652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273164PMC
June 2021

The ETS Inhibitor YK-4-279 Suppresses Thyroid Cancer Progression Independent of Promoter Mutations.

Front Oncol 2021 16;11:649323. Epub 2021 Jun 16.

Department of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Hotspot mutations in the core promoter region of the () gene have been well established to associate with aggressive clinical characteristics, radioiodine refractory, tumor recurrence, and mortality in thyroid cancer. Several E-twenty-six (ETS) transcription factors were reported to selectively bound to the mutant promoter and activated TERT expression. In this study we aimed to investigate whether promoter mutations confer sensitivity to ETS inhibitor YK-4-279 in thyroid cancer cells and whether this inhibitor could be served as a potential therapeutic agent for thyroid cancer. assays showed that YK-4-279 treatment sharply suppressed cell viability, colony formation, migration, and invasion, as well as induced cell cycle arrest and apoptosis in a panel of thyroid cancer cells. The cell viability after YK-4-279 treatment was similar between cell lines harboring mutant and wild-type promoters. Furthermore, YK-4-279 treatment reduced both luciferase activity and mRNA expression of TERT independent of promoter mutation status. Data from RNA-seq further revealed that YK-4-279 significantly affected biological processes including DNA replication and cell cycle. Reduced DNA helicase activity and decreased expression of several helicase genes were observed after YK-4-279 treatment. Moreover, YK-4-279 significantly inhibited tumor growth and induced apoptosis in a xenograft mice model. Thus, ETS inhibitor YK-4-279 suppressed TERT expression and conferred anti-tumor activity in a promoter mutation-independent manner, and it could be a potential agent for the treatment of advanced thyroid cancers.
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http://dx.doi.org/10.3389/fonc.2021.649323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242932PMC
June 2021

Comparison of Clinical Features between Primary Aldosteronism and Essential Hypertension in Chinese Patients: A Case-Control Study.

Int J Endocrinol 2021 7;2021:6685469. Epub 2021 Jun 7.

Endocrinology Department, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Primary aldosteronism (PA) is one of the most common forms of secondary hypertension. Recent studies suggest that, compared with essential hypertension (EH), PA presents more severe disorders of glycolipid metabolism and organ damages. This case-control retrospective study aimed to ascertain clinical features and metabolic parameters between Chinese patients of PA and EH. 174 PA patients and 174 matched EH patients were recruited. Their clinical features, biochemistry parameters, the ventricular septal thickness, and left ventricular mass index (LVMI) were compared. HOMA-% and HOMA-IR were calculated to evaluate glucose metabolism. The results showed that there was no significant difference regarding BMI, waist-to-hip ratio, and blood pressure between the two groups. The blood potassium level was significantly lower in PA patients than those in EH patients. The abnormal glucose tolerance and the incidence of diabetes in the PA group were not significantly different from those in EH group, but the insulin secretion levels at 0 min and 30 min were significantly weaker than those in the EH group, and the HOMA-% was also lower in the PA group than those in the EH group. Left ventricular structural abnormalities in PA patients were more severe than those in EH patients. Subtype analysis indicated that patient with aldosterone-producing adenoma (APA) has more serious hypokalemia and lower levels of HOMA-% and HOMA-IR comparing to those in the idiopathic adrenal hyperplasia (IHA) patient. These findings demonstrated that PA patients showed more impaired insulin secretion function and more severe left ventricular structural damage compared with EH patients.
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http://dx.doi.org/10.1155/2021/6685469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203403PMC
June 2021

Genome-Wide Histone H3K27 Acetylation Profiling Identified Genes Correlated With Prognosis in Papillary Thyroid Carcinoma.

Front Cell Dev Biol 2021 11;9:682561. Epub 2021 Jun 11.

Department of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Thyroid carcinoma (TC) is the most common endocrine malignancy, and papillary TC (PTC) is the most frequent subtype of TC, accounting for 85-90% of all the cases. Aberrant histone acetylation contributes to carcinogenesis by inducing the dysregulation of certain cancer-related genes. However, the histone acetylation landscape in PTC remains elusive. Here, we interrogated the epigenomes of PTC and benign thyroid nodule (BTN) tissues by applying H3K27ac chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) along with RNA-sequencing. By comparing the epigenomic features between PTC and BTN, we detected changes in H3K27ac levels at active regulatory regions, identified PTC-specific super-enhancer-associated genes involving immune-response and cancer-related pathways, and uncovered several genes that associated with disease-free survival of PTC. In summary, our data provided a genome-wide landscape of histone modification in PTC and demonstrated the role of enhancers in transcriptional regulations associated with prognosis of PTC.
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http://dx.doi.org/10.3389/fcell.2021.682561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226268PMC
June 2021

Utility of multi-parametric quantitative magnetic resonance imaging of the lacrimal gland for diagnosing and staging Graves' ophthalmopathy.

Eur J Radiol 2021 Aug 8;141:109815. Epub 2021 Jun 8.

Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong Province, China. Electronic address:

Purpose: To explore radiological changes of the lacrimal gland (LG) in Graves' ophthalmopathy (GO) based on multi-parametric quantitative MRI and its clinical utility in LG diagnosis and activity in GO.

Methods: We enrolled 99 consecutive patients with GO (198 eyes) and 12 Graves' Disease (GD) patients (24 eyes) from July 2018 to June 2020. Clinical, laboratory, and MRI data were collected at the first visit. Based on clinical activity scores, eyes with GO were subdivided into active and inactive groups. T2-relaxation time (T2) and the absolute reduction in T1-relaxation time (ΔT1) were determined. After MRI and processing, we performed descriptive data analysis and group comparisons. Novel logistic regression predictive models were developed for diagnosing and staging GO. Diagnostic performance of MRI parameters and models was assessed by receiver operating characteristic curve analysis.

Results: LG in GO group had significantly higher T2 and ΔT1 values than the GD group [106.25(95.30,120.21) vs. 83.35(78.15,91.45), P<0.001, and 662.62(539.33,810.95) vs. 547.35(458.62,585.57), P = 0.002, respectively]. The GO group had higher T2 of LG indicating higher disease activity [110.93(102.54,127.67) vs. 93.29(87.06,101.96), P < 0.001]. Combining T2 and ΔT1 values of LG, Model I had higher diagnostic value for distinguishing GO from GD (AUC=0.94, 95 %CI: 0.89,0.99, P<0.001). Meanwhile, T2 of LG had higher diagnostic value for grading GO activity (AUC = 0.84, 95 %CI: 0.76,0.92, P<0.001).

Conclusions: Multi-parametric quantitative MRI parameters of the LG in GO were significantly altered. Novel models combining LG T2 and ΔT1 values showed excellent predictive performances in diagnosing GO. Furthermore, T2 of LG showed practical utility for staging GO.
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http://dx.doi.org/10.1016/j.ejrad.2021.109815DOI Listing
August 2021

Selenite Induces Cell Cycle Arrest and Apoptosis Reactive Oxygen Species-Dependent Inhibition of the AKT/mTOR Pathway in Thyroid Cancer.

Front Oncol 2021 21;11:668424. Epub 2021 May 21.

Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Thyroid cancer is the most common endocrine malignancy, and its incidence has increased in the past decades. Selenium has been shown to have therapeutic effects against several tumors. However, its role in thyroid cancer and its underlying molecular mechanism remains to be explored. In the present study, we demonstrated that sodium selenite significantly decreased cell viability and induced G0/G1 cell cycle arrest and apoptosis in thyroid cancer cells in a dose-dependent manner. Transcriptomics revealed that sodium selenite induced intracellular reactive oxygen species (ROS) by promoting oxidative phosphorylation. Increased intracellular ROS levels inhibited the AKT/mTOR signaling pathway and upregulated EIF4EBP3. Intracellular ROS inhibition by N-acetylcysteine (NAC) ameliorated the cellular effects of sodium selenite. The findings were reproduced in xenograft thyroid tumor models. Our data demonstrated that sodium selenite exhibits strong anticancer effects against thyroid cancer cells, which involved ROS-mediated inhibition of the AKT/mTOR pathway. This suggests that sodium selenite may serve as a therapeutic option for advanced thyroid cancer.
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http://dx.doi.org/10.3389/fonc.2021.668424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176115PMC
May 2021

Metformin protects against insulin resistance induced by high uric acid in cardiomyocytes via AMPK signalling pathways in vitro and in vivo.

J Cell Mol Med 2021 Jul 30;25(14):6733-6745. Epub 2021 May 30.

Department of Cardiology, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.

High uric acid (HUA) is associated with insulin resistance (IR) in cardiomyocytes. We investigated whether metformin protects against HUA-induced IR in cardiomyocytes. We exposed primary cardiomyocytes to HUA, and cellular glucose uptake was quantified by measuring the uptake of 2-NBDG, a fluorescent glucose analog. Western blot was used to examine the levels of signalling protein. Membrane of glucose transporter type 4 (GLUT4) was analysed by immunofluorescence. We monitored the impact of metformin on HUA-induced IR and in myocardial tissue of an acute hyperuricaemia mouse model established by potassium oxonate treatment. Treatment with metformin protected against HUA-reduced glucose uptake induced by insulin in cardiomyocytes. HUA directly inhibited the phosphorylation of Akt and the translocation of GLUT4 induced by insulin, which was blocked by metformin. Metformin promoted phosphorylation of AMP-activated protein kinase (AMPK) and restored the insulin-stimulated glucose uptake in HUA-induced IR cardiomyocytes. As a result of these effects, in a mouse model of acute hyperuricaemia, metformin improved insulin tolerance and glucose tolerance, accompanied by increased AMPK phosphorylation, Akt phosphorylation and translocation of GLUT4 in myocardial tissues. As expected, AICAR, another AMPK activator, had similar effects to metformin, demonstrating the important role of AMPK activation in protecting against IR induced by HUA in cardiomyocytes. Metformin protects against IR induced by HUA in cardiomyocytes and improves insulin tolerance and glucose tolerance in an acute hyperuricaemic mouse model, along with the activation of AMPK. Consequently, metformin may be an important potential new treatment strategy for hyperuricaemia-related cardiovascular disease.
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http://dx.doi.org/10.1111/jcmm.16677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278091PMC
July 2021

Effect of microbial and chemical additives on the fermentation and aerobic stability of alfalfa silage ensiled at 2 dry matters and subjected to air stress during storage.

J Anim Sci 2021 Jul;99(7)

Department of Animal and Food Sciences, University of Delaware, Newark 19716, USA.

We evaluated the effects of different types of additives on the fermentation and aerobic stability of alfalfa (Medicago sativa) ensiled at 2 dry matters (DM). Alfalfa was untreated (CTRL) or treated with sodium benzoate, potassium sorbate, and sodium nitrite (SFE), or microbial inoculants (Lactobacillus plantarum MTD1 [LP] or L. buchneri 40788 and Pediococcus pentocaseus 12455 [LBPP]) at a moderate (38%) and high (46%) DM using a completely randomized design with a 2 × 4 factorial arrangement of treatments. High DM silage was higher (P < 0.01) in pH, had less lactic and acetic acid (P < 0.01) and had more yeasts (P < 0.05) and molds (P < 0.01) than moderate DM silage. Recovery of DM declined (P < 0.01) for CTRL and LP treated silages with increasing DM but was not different between LBPP and SFE treatments. Compared to CTRL, LBPP had a lower (P < 0.01) DM recovery at the moderate DM, but SFE had the greatest (P < 0.01) recovery of all treatments at the high DM. Treatment with LBPP increased (P < 0.05) the concentrations of acetic acid and 1,2 propanediol (PD) compared with other treatments (P < 0.01). Numerically, fewer yeasts were found in additive treated silages compared with CTRL, but they were statistically (P < 0.01) lower only when treated with SFE. Treatment with LP resulted in a small improvement in aerobic stability at the moderate but not high DM. In contrast, treatment with SFE and LBPP markedly improved (P < 0.01) the aerobic stability of alfalfa silage at both DM. Whereas SFE and LBPP were similar in their improvements in aerobic stability at the DM, LBPP was better (P < 0.01) than SFE at the high DM. A higher (P < 0.01) concentration of acetic acid in LBPP compared with other treatments was most likely responsible for better stability. This study showed that LBPP and SFE resulted in increases in the aerobic stability of alfalfa silage and it is the first study showing SFE, can markedly improve the aerobic stability of alfalfa silage.
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http://dx.doi.org/10.1093/jas/skab174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315128PMC
July 2021

Safety measures for COVID-19 do not compromise the outcomes of patients undergoing primary percutaneous coronary intervention: a single center retrospective study.

Sci Rep 2021 05 11;11(1):9959. Epub 2021 May 11.

Center of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, 5 Jingyuan Road, Beijing, 100043, China.

Coronavirus disease 2019 (COVID-19) is a global pandemic impacting nearly 170 countries/regions and millions of patients worldwide. Patients with acute myocardial infarction (AMI) still need to be treated at percutaneous coronary intervention (PCI) centers with relevant safety measures. This retrospective study was conducted to assess the therapeutic outcomes of PCI performed under the safety measures and normal conditions. AMI patients undergoing PCI between January 24 to April 30, 2020 were performed under safety measures for COVID-19. Patients received pulmonary computed tomography (CT) and underwent PCI in negative pressure ICU. Cardiac catheterization laboratory (CCL) staff and physicians worked with level III personal protection. Demographic and clinical data, such as door-to-balloon (DTB) time, operation time, complications for patients in this period (COVID-19 group) and the same period in 2019 (2019 group) were retrieved and analyzed. COVID-19 and 2019 groups had 37 and 96 patients, respectively. There was no significant difference in age, gender, BMI and comorbidity between the two groups. DTB time and operation time were similar between the two groups (60.0 ± 12.39 vs 58.83 ± 12.85 min, p = 0.636; 61.46 ± 9.91 vs 62.55 ± 10.72 min, p = 0.592). Hospital stay time in COVID-19 group was significantly shorter (6.78 ± 2.14 vs 8.85 ± 2.64 days, p < 0.001). The incidences of malignant arrhythmia and Takotsubo Syndrome in COVID-19 group were higher than 2019 group significantly (16.22% vs 5.21%, p = 0.039; 10.81% vs 1.04% p = 0.008). During hospitalization and 3-month follow-up, the incidence of major adverse cardiovascular events and mortality in the two groups were statistically similar (35.13% vs 14.58%, p = 0.094; 16.22% vs 8.33%, p = 0.184). The risk of major adverse cardiac events (MACE) was associated with cardiogenic shock (OR, 11.53; 95% CI, 2.888-46.036; p = 0.001), malignant arrhythmias (OR, 7.176; 95% CI, 1.893-27.203; p = 0.004) and advanced age (≥ 75 years) (OR, 6.718; 95% CI, 1.738-25.964; p = 0.006). Cardiogenic shock (OR, 17.663; 95% CI, 5.5-56.762; p < 0.001) and malignant arrhythmias (OR, 4.659; 95% CI, 1.481-14.653; p = 0.008) were also associated with death of 3 months. Our analysis showed that safety measures undertaken in this hospital, including screening of COVID-19 infection and use of personal protection equipment for conducting PCI did not compromise the surgical outcome as compared with PCI under normal condition, although there were slight increases in incidence of malignant arrhythmia and Takotsubo Syndrome.
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http://dx.doi.org/10.1038/s41598-021-89419-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113542PMC
May 2021

A Glycolysis-Related Five-Gene Signature Predicts Biochemical Recurrence-Free Survival in Patients With Prostate Adenocarcinoma.

Front Oncol 2021 19;11:625452. Epub 2021 Apr 19.

Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Prostate cancer (PCa) is one of the most frequently diagnosed cancers in males worldwide. Approximately 25% of all patients experience biochemical recurrence (BCR) after radical prostatectomy (RP) and BCR indicates increased risk for metastasis and castration resistance. PCa patients with highly glycolytic tumors have a worse prognosis. Thus, this study aimed to explore glycolysis-based predictive biomarkers for BCR. Expression data and clinical information of PCa samples were retrieved from three publicly available datasets. One from The Cancer Genome Atlas (TCGA) dataset was used as the training cohort, and two from the Gene Expression Omnibus (GEO) dataset (GSE54460 and GSE70769) were used as validation cohorts. Using the training cohort, univariate Cox regression survival analysis, robust likelihood-based survival model, and stepwise multiply Cox analysis were sequentially applied to explore predictive glycolysis-related candidates. A five-gene risk score was then constructed based on the Cox coefficient as the following: (-0.8367*GYS2) + (0.3448*STMN1) + (0.3595*PPFIA4) + (-0.1940*KDELR3) + (0.4779*ABCB6). Receiver operating characteristic curve (ROC) analysis was used to identify the optimal cut-off point, and patients were divided into low risk and high risk groups. Kaplan-Meier analysis revealed that high risk group had significantly shorter BCR free survival time as compared with that in low risk group in training and validation cohorts. In conclusion, our data support the glycolysis-based five-gene signature as a novel and robust signature for predicting BCR of PCa patients.
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http://dx.doi.org/10.3389/fonc.2021.625452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092437PMC
April 2021

Genetic and biological properties of H7N9 avian influenza viruses detected after application of the H7N9 poultry vaccine in China.

PLoS Pathog 2021 04 27;17(4):e1009561. Epub 2021 Apr 27.

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, People's Republic of China.

The H7N9 avian influenza virus (AIV) that emerged in China have caused five waves of human infection. Further human cases have been successfully prevented since September 2017 through the use of an H7N9 vaccine in poultry. However, the H7N9 AIV has not been eradicated from poultry in China, and its evolution remains largely unexplored. In this study, we isolated 19 H7N9 AIVs during surveillance and diagnosis from February 2018 to December 2019, and genetic analysis showed that these viruses have formed two different genotypes. Animal studies indicated that the H7N9 viruses are highly lethal to chicken, cause mild infection in ducks, but have distinct pathotypes in mice. The viruses bound to avian-type receptors with high affinity, but gradually lost their ability to bind to human-type receptors. Importantly, we found that H7N9 AIVs isolated in 2019 were antigenically different from the H7N9 vaccine strain that was used for H7N9 influenza control in poultry, and that replication of these viruses cannot, therefore, be completely prevented in vaccinated chickens. We further revealed that two amino acid mutations at positions 135 and 160 in the HA protein added two glycosylation sites and facilitated the escape of the H7N9 viruses from the vaccine-induced immunity. Our study provides important insights into H7N9 virus evolution and control.
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http://dx.doi.org/10.1371/journal.ppat.1009561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104392PMC
April 2021

Highly Pathogenic Avian Influenza A(H5N8) Virus in Swans, China, 2020.

Emerg Infect Dis 2021 06 9;27(6):1732-1734. Epub 2021 Apr 9.

In October 2020, highly pathogenic avian influenza A(H5N8) viruses were detected in 2 dead swans in Inner Mongolia, China. Genetic analysis showed that the H5N8 isolates belong to clade 2.3.4.4b and that the isolates cluster with the H5N8 viruses isolated in Eurasia in the fall of 2020.
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http://dx.doi.org/10.3201/eid2706.204727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153893PMC
June 2021

Glucose-dependent insulinotropic polypeptide modifies adipose plasticity and promotes beige adipogenesis of human omental adipose-derived stem cells.

FASEB J 2021 05;35(5):e21534

Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

The adipocyte precursors (APs) located in white adipose tissue (WAT) are functionally significant in adipose plasticity and browning. Modifying adipogenesis or WAT browning targeted on APs is a promising mechanism for anti-obesity drug. We herein explored the in vitro actions and mechanisms of glucose-dependent insulinotropic polypeptide (GIP), a gut-derived peptide, in human adipose-derived mesenchymal stem cells (hADSCs) isolated from omentum. The hADSCs were cotreated with 100 nM GIP with or without equimolar concentration of GIP3-42 (a GIP receptor antagonist), and subsequently examined in vitro. CCK-8, EdU incorporation, and flow cytometry assays were used to assess cellular proliferation. Annexin V FTIC/PI double stain, TUNEL staining, and Western blot were applied for apoptosis evaluation. Adipogenesis was reflected by Western blot, real-time PCR, Oil Red O staining, mitochondrial staining, and mitochondrial DNA analysis. Results showed that GIP promoted proliferation and inhibited apoptosis of hADSCs via pleiotropic effects. Besides, GIP facilitated de novo beige adipogenesis, by accelerating mitotic clonal expansion (MCE), upregulating core adipogenic regulators (C/EBPα and PPARγ), augmenting beige-related genes (UCP1, PGC1α, and PRDM16), increasing mitochondrial content and improving beige adipocyte functionalities. Above all, our study expands knowledge on the mechanisms of GIP modifying adipogenesis especially in inducing beige adipogenesis, and thus provides a theoretical support for clinical usage of GIP on obesity treatment.
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http://dx.doi.org/10.1096/fj.201903253RDOI Listing
May 2021

Deep learning-based artificial intelligence model to assist thyroid nodule diagnosis and management: a multicentre diagnostic study.

Lancet Digit Health 2021 04;3(4):e250-e259

Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address:

Background: Strategies for integrating artificial intelligence (AI) into thyroid nodule management require additional development and testing. We developed a deep-learning AI model (ThyNet) to differentiate between malignant tumours and benign thyroid nodules and aimed to investigate how ThyNet could help radiologists improve diagnostic performance and avoid unnecessary fine needle aspiration.

Methods: ThyNet was developed and trained on 18 049 images of 8339 patients (training set) from two hospitals (the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, and Sun Yat-sen University Cancer Center, Guangzhou, China) and tested on 4305 images of 2775 patients (total test set) from seven hospitals (the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; the Guangzhou Army General Hospital, Guangzhou, China; the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; the First Affiliated Hospital of Sun Yat-sen University; Sun Yat-sen University Cancer Center; and the First Affiliated Hospital of Guangxi Medical University, Nanning, China) in three stages. All nodules in the training and total test set were pathologically confirmed. The diagnostic performance of ThyNet was first compared with 12 radiologists (test set A); a ThyNet-assisted strategy, in which ThyNet assisted diagnoses made by radiologists, was developed to improve diagnostic performance of radiologists using images (test set B); the ThyNet assisted strategy was then tested in a real-world clinical setting (using images and videos; test set C). In a simulated scenario, the number of unnecessary fine needle aspirations avoided by ThyNet-assisted strategy was calculated.

Findings: The area under the receiver operating characteristic curve (AUROC) for accurate diagnosis of ThyNet (0·922 [95% CI 0·910-0·934]) was significantly higher than that of the radiologists (0·839 [0·834-0·844]; p<0·0001). Furthermore, ThyNet-assisted strategy improved the pooled AUROC of the radiologists from 0·837 (0·832-0·842) when diagnosing without ThyNet to 0·875 (0·871-0·880; p<0·0001) with ThyNet for reviewing images, and from 0·862 (0·851-0·872) to 0·873 (0·863-0·883; p<0·0001) in the clinical test, which used images and videos. In the simulated scenario, the number of fine needle aspirations decreased from 61·9% to 35·2% using the ThyNet-assisted strategy, while missed malignancy decreased from 18·9% to 17·0%.

Interpretation: The ThyNet-assisted strategy can significantly improve the diagnostic performance of radiologists and help reduce unnecessary fine needle aspirations for thyroid nodules.

Funding: National Natural Science Foundation of China and Guangzhou Science and Technology Project.
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http://dx.doi.org/10.1016/S2589-7500(21)00041-8DOI Listing
April 2021

IL-38 Exerts Anti-Inflammatory and Antifibrotic Effects in Thyroid-Associated Ophthalmopathy.

J Clin Endocrinol Metab 2021 Jul;106(8):e3125-e3142

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.

Context: Thyroid-associated ophthalmopathy (TAO) is an organ-specific autoimmune disease closely associated with Graves' disease. IL-38, a novel cytokine in the IL-1 superfamily, has been reported to be involved in the pathogenesis of various autoimmune diseases.

Objective: We aimed to evaluate the relationship between IL-38 and TAO disease activity and its role in inflammation and fibrosis in TAO.

Methods: Blood samples and orbital connective tissues were collected from TAO patients and controls. Orbital fibroblasts were isolated from patients with TAO. Enzyme-linked immunosorbent assay, immunohistochemistry, flow cytometry, immunofluorescence, quantitative real-time PCR and Western blot analysis were performed.

Results: Here, we demonstrated that IL-38 levels decreased in the circulation and orbital connective tissues of patients with TAO compared with the controls, and levels were negatively correlated with the clinical activity score. In vitro, potent anti-inflammatory and antifibrotic effects of IL-38 were observed. Furthermore, we revealed that IL-38 can counteract the phosphorylation of star molecules in multiple classical pathways.

Conclusion: IL-38 plays a protective role in TAO and is associated with its pathogenesis. Our data suggest that IL-38 may be a promising marker of TAO disease activity and a potential target for TAO therapy.
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http://dx.doi.org/10.1210/clinem/dgab154DOI Listing
July 2021

SLC6A15 acts as a tumor suppressor to inhibit migration and invasion in human papillary thyroid cancer.

J Cell Biochem 2021 Aug 10;122(8):814-826. Epub 2021 Mar 10.

Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.

Solute Carrier Family 6 Member 15 (SLC6A15), a sodium-dependent neutral amino acid transporter, has been found with dysregulated expression in several kinds of cancers. However, the expression pattern and the biological functions of SLC6A15 in papillary thyroid cancer (PTC) remain unknown. In this study, we found that SLC6A15 was downregulated in PTC, which was related to N classification. Ectopic overexpression of SLC6A15 impaired migratory and invasive abilities of PTC cell in vitro. In addition, we identified intercellular adhesion molecule-1, a vital oncogene in thyroid cancer progression, was involved in the effects of SLC6A15 on PTC cell. These results indicate that SLC6A15 acts as a tumor suppressor and might be a potential therapeutic target in the treatment of PTC.
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http://dx.doi.org/10.1002/jcb.29914DOI Listing
August 2021

Synergistic integration of dihydro-artemisinin with γ-aminobutyric acid results in a more potential anti-depressant.

Bioorg Chem 2021 May 25;110:104769. Epub 2021 Feb 25.

Institute of Traditional Chinese Medicine and Natural Product, College of Pharmacy, Jinan University, Guangzhou 510632, PR China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Guangzhou 510632, PR China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education, School of Pharmacy, Jinan University, Guangzhou 510632, PR China. Electronic address:

Three hybrids of dihydro-artemisinin (DHA) with β-aminopropionic acid, γ-aminobutyric acid, and histamine have been designed and synthesized. The conjugate of DHA with GABA labelled as 5b was confirmed the most active candidate against both Cort- and SNP-induced PC12 cell impairments with EC value of 8.04 ± 0.35, and 9.38 ± 0.56 μM, respectively. 5b was clearly highlighted as a good modulator on protein expression of Akt, Bcl-2, and Bax, indicating its functions against programmed cell apoptosis. 5b significantly reversed the Cort-induced excessive calcium influx and release from internal organelles. It was demonstrated the ability to express increased levels of β-tubulin III and to up-regulate phosphorylation level of cAMP response element-binding protein (CREB), leading to cell differentiation. It can penetrate blood - brain barrier (BBB) with propriate stability. Altogether, these data strongly support that 5b is a potential anti-depressant.
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http://dx.doi.org/10.1016/j.bioorg.2021.104769DOI Listing
May 2021

Long Non-coding RNA GAS5 Worsens Coronary Atherosclerosis Through MicroRNA-194-3p/TXNIP Axis.

Mol Neurobiol 2021 Jul 27;58(7):3198-3207. Epub 2021 Feb 27.

Cardiac Rehabilitation Center, Beijing Rehabilitation Hospital, Capital Medical University, Xixiazhuang, Badachu Road, Shijingshan Distract, Beijing, 100144, China.

It is formerly conducted that long non-coding RNA growth arrest-specific 5 (GAS5) is involved in the process of coronary atherosclerosis (AS). The regulatory effects of GAS5 on the microRNA (miR)-194-3p/thioredoxin-interacting protein (TXNIP) axis in AS have been insufficiently explored yet. Thereafter, this work is started from GAS5/miR-194-3p/TXNIP axis in AS. AS rats were modeled to obtain their coronary vascular tissues and endothelial cells (ECs), in which GAS5, miR-194-3p, and TXNIP expression were tested. ECs were identified by immunohistochemistry. The mechanism among GAS5, miR-194-3p, and TXNIP was determined. ECs were transfected with inhibited GAS5 or overexpressed miR-194-3p to decipher their functions in proliferation and apoptosis of ECs in AS. Raised GAS5 and TXNIP and degraded miR-194-3p expression levels exhibited in AS. GAS5 bound to miR-194-3p while miR-194-3p targeted TXNIP. Depleting GAS5 or restoring miR-194-3p enhanced proliferation and depressed apoptosis of ECs in AS. This work clearly manifests that inhibited GAS5 facilitates the growth of ECs through miR-194-3p-targeted TXNIP in AS, consolidating the basal reference to the curing for AS.
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http://dx.doi.org/10.1007/s12035-021-02332-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257541PMC
July 2021

Single-cell transcriptomic landscape reveals the differences in cell differentiation and immune microenvironment of papillary thyroid carcinoma between genders.

Cell Biosci 2021 Feb 15;11(1):39. Epub 2021 Feb 15.

Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road II, Guangdong, 510080, Guangzhou, China.

Background: Papillary thyroid carcinoma (PTC) is the main pathological type of thyroid carcinoma (TC). Gender is a prominent background parameter for patients with PTC. Here, we aimed to delineate the differences in cell clusters and immune microenvironment in relation to gender in PTC.

Methods: We generated 6720, 14,666, and 33,373 single-cell transcriptomes that were pooled from the tissues of four male patients with PTC, seven female patients with PTC, and three patients with nodular goiter, respectively. We performed single-cell RNA-sequencing (scRNA-seq) based on BD Rhapsody and characterized the first single-cell transcriptomic landscape of PTC involving gender. The differential cell clusters and their gene profiles were identified and analyzed via a multi-resolution network in male and female patients. The interactions of fibroblasts and endothelial cells with malignant epithelial cells and the difference in the immune infiltration of B and T lymphocytes according to gender were assessed.

Results: Malignant epithelial cells were divided into two distinct subsets in male and female patients with PTC. Moreover, significant differences involving inferred copy-number variations (CNVs), gene profiles, and cell differentiation were detected between male and female patients. Regarding the interactions of fibroblasts and endothelial cells with malignant epithelial cells, members of the human leukocyte antigen (HLA) family and their receptors were considered as typical in female patients with PTC, while transforming growth factor beta 1 (TGFB1) and its receptors were typical of male patients with PTC. The characteristics of B cells, including cell clusters, cell differentiation, and dominant gene sets, were significantly different between genders.

Conclusions: Our data revealed the detailed differences in cell clusters and immune microenvironment in PTC according to gender at the single-cell level, which provided new insights into the understanding of the impact of gender on PTC.
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http://dx.doi.org/10.1186/s13578-021-00549-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885238PMC
February 2021

Heterozygosity for a Pathogenic Variant in That Causes Autosomal Recessive Gitelman Syndrome Is Associated with Lower Serum Potassium.

J Am Soc Nephrol 2021 Mar 4;32(3):756-765. Epub 2021 Feb 4.

Program in Personalized and Genomic Medicine, Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland

Background: Potassium levels regulate multiple physiologic processes. The heritability of serum potassium level is moderate, with published estimates varying from 17% to 60%, suggesting genetic influences. However, the genetic determinants of potassium levels are not generally known.

Methods: A whole-exome sequencing association study of serum potassium levels in 5812 subjects of the Old Order Amish was performed. A dietary salt intervention in 533 Amish subjects estimated interaction between p.R642G and sodium intake.

Results: A cluster of variants, spanning approximately 537 kb on chromosome 16q13, was significantly associated with serum potassium levels. Among the associated variants, a known pathogenic variant of autosomal recessive Gitelman syndrome (p.R642G ) was most likely causal; there were no homozygotes in our sample. Heterozygosity for p.R642G was also associated with lower chloride levels, but not with sodium levels. Notably, p.R642G showed a novel association with lower serum BUN levels. Heterozygotes for p.R642G had a two-fold higher rate of self-reported bone fractures and had higher resting heart rates on a low-salt diet compared with noncarriers.

Conclusions: This study provides evidence that heterozygosity for a pathogenic variant in causing Gitelman syndrome, a canonically recessive disorder, contributes to serum potassium concentration. The findings provide insights into biology and the effects of heterozygosity on electrolyte homeostasis and related subclinical phenotypes that may have implications for personalized medicine and nutrition.
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http://dx.doi.org/10.1681/ASN.2020071030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920171PMC
March 2021

Genetic characteristics and pathogenicity of novel reassortant H6 viruses isolated from wild birds in China.

Vet Microbiol 2021 Mar 6;254:108978. Epub 2021 Jan 6.

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China. Electronic address:

During our routine surveillance, we isolated seven H6 avian influenza virus (AIV) strains, including three H6N1 strains, three H6N2 strains, and one H6N8 strain, from 3667 fresh fecal samples that were collected from wild bird habitats in China from March 2017 and May 2019. Phylogenetic analysis revealed that these viruses formed five different genotypes and have undergone complicate reassortment during their evolution by acquiring genes from AIVs of both Eurasian and North American lineages that have been previously detected in migrating waterfowl and poultry. Viral pathogenesis in mice showed that these H6 viruses replicated efficiently in both the nasal turbinates and lungs of mice without pre-adaptation, but none of them were lethal for mice. We studied the genetic characteristic and biological property of novel reassortant H6 viruses isolated from wild birds in China. It also highlights the need for continued surveillance of H6 AIVs circulating in nature.
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http://dx.doi.org/10.1016/j.vetmic.2021.108978DOI Listing
March 2021

Narrative review of the choices of stem cell sources and hydrogels for cartilage tissue engineering.

Ann Transl Med 2020 Dec;8(23):1598

Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Stem cell-based therapy is a promising treatment for cartilage defects due to the pluripotency, abundant sources and low immunogenicity of stem cells. Hydrogels are a promising class of biomaterials for cartilage engineering and are characterized by bioactivity, degradability and elasticity as well as provide water content and mechanical support. The combination of stem cells and hydrogels opens new possibilities for cartilage tissue engineering. However, the selection of suitable types of stem cells and hydrogels is difficult. Currently, various types of stem cells, such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and peripheral blood mononuclear cells (PBMSCs), and various types of hydrogels, including natural polymers, chemically modified natural polymers and synthetic polymers, have been explored based on their potential for cartilage tissue engineering. These materials are used independently or in combination; however, there is no clear understanding of their merits and disadvantages with regard to their suitability for cartilage repair. In this article, we aim to review recent progress in the use of stem cell-hydrogel hybrid constructs for cartilage tissue engineering. We focus on the effects of stem cell types and hydrogel types on efficient chondrogenesis from cellular, preclinical and clinical perspectives. We compare and analyze the advantages and disadvantages of these cells and hydrogels with the hope of increasing discussion of their suitability for cartilage repair and present our perspective on their use for the improvement of physical and biological properties for cartilage tissue engineering.
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http://dx.doi.org/10.21037/atm-20-2342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791208PMC
December 2020

Henagliflozin monotherapy in patients with type 2 diabetes inadequately controlled on diet and exercise: A randomized, double-blind, placebo-controlled, phase 3 trial.

Diabetes Obes Metab 2021 05 31;23(5):1111-1120. Epub 2021 Jan 31.

Jiangsu Hengrui Medicine Co. Ltd, Shanghai, China.

Aim: To evaluate henagliflozin, a novel sodium-glucose co-transporter-2 inhibitor, as monotherapy in patients with type 2 diabetes and inadequate glycaemic control with diet and exercise.

Materials And Methods: This multicentre trial included a 24-week, randomized, double-blind, placebo-controlled period, followed by a 28-week extension period. Four hundred and sixty-eight patients with an HbA1c of 7.0%-10.5% were randomly assigned (1:1:1) to receive once-daily placebo, or 5 or 10 mg henagliflozin. After 24 weeks, patients on placebo were switched to 5 or 10 mg henagliflozin, and patients on henagliflozin maintained the initial therapy. The primary endpoint was the change in HbA1c from baseline after 24 weeks.

Results: At Week 24, the placebo-adjusted least squares (LS) mean changes from baseline in HbA1c were -0.91% (95% CI: -1.11% to -0.72%; P < .001) and -0.94% (-1.13% to -0.75%; P < .001) with henagliflozin 5 and 10 mg, respectively; the placebo-adjusted LS mean changes were -1.3 (-1.8 to -0.9) and -1.5 (-2.0 to -1.1) kg in body weight, and -5.1 (-7.2 to -3.0) and -4.4 (-6.5 to -2.3) mmHg in systolic blood pressure (all P < .05). The trends of these improvements were sustained for an additional 28 weeks. Adverse events occurred in 81.0%, 78.9% and 78.9% of patients in the placebo, henagliflozin 5 and 10 mg groups, respectively. No diabetic ketoacidosis or major episodes of hypoglycaemia occurred.

Conclusions: Henagliflozin 5 mg and 10 mg as monotherapy provided effective glycaemic control, reduced body weight and blood pressure, and was generally well tolerated.
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http://dx.doi.org/10.1111/dom.14314DOI Listing
May 2021

Translation and validation of the Chinese version of medical maximizer-minimizer scale: a cross-sectional study.

BMJ Open 2021 01 6;11(1):e042432. Epub 2021 Jan 6.

Department of Geriatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

Objective: Medical overutilisation and underutilisation affect optimal healthcare. The Medical Maximizer-Minimizer Scale (MMS) was developed to assess individual medical maximising and minimising tendencies. Despite significant improvement in the healthcare system over the past four decades, no psychometric scales to examine treatment maximising and minimising preferences are available in China. This study aimed to translate the MMS into Chinese and examine its reliability and validity in a Chinese population.

Design: This cross-sectional study was conducted in December 2019 through an online survey panel.

Methods: The MMS was translated into a Chinese version (CN-MMS) using a forward-backward translation procedure. Next, a random online survey of the general population in China was conducted. Exploratory factor analysis (EFA) and confirmatory factor analysis were performed to examine the underlying factor structure of the CN-MMS. The internal consistency reliability of the scale was determined using Cronbach's α coefficient and corrected item-total correlation. A multivariate linear regression analysis was used to examine associations between medical maximising and minimising preferences and demographic variables in the Chinese population.

Results: This study included 984 participants aged 18-80 years. The CN-MMS retained 10 items, and the EFA supported a two-factor structure. The model fit for this two-factor structure of the CN-MMS was acceptable with χ/df=3.7, comparative fit index=0.958, goodness-of-fit index=0.951, Tucker-Lewis Index=0.944 and root mean square error of approximation=0.074. The scale had a Cronbach's α coefficient of 0.864, corrected item-total correlation of 0.451-0.667, and test-retest reliability of 0.815. Significant predictors of CN-MMS total score were nationality and household monthly income.

Conclusions: The CN-MMS showed satisfactory psychometric properties. Therefore, it can be used to investigate the individual medical maximising and minimising tendencies among the general Chinese population.
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http://dx.doi.org/10.1136/bmjopen-2020-042432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789444PMC
January 2021

Conjugation of tacrine with genipin derivative not only enhances effects on AChE but also leads to autophagy against Alzheimer's disease.

Eur J Med Chem 2021 Feb 2;211:113067. Epub 2020 Dec 2.

Institute of Traditional Chinese Medicine and Natural Product, College of Pharmacy, Jinan University, Guangzhou, 510632, PR China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Guangzhou, 510632, PR China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education, School of Pharmacy, Jinan University, Guangzhou, 510632, PR China. Electronic address:

Seven tacrine/CHR21 conjugates have been designed and synthesized. Compound 8-7 was confirmed as the most active AChE inhibitor with IC value of 5.8 ± 1.4 nM, which was 7.72-fold stronger than tacrine. It was also shown as a strong BuChE inhibitor (IC value of 3.7 ± 1.3 nM). 8-7 was clearly highlighted not only as an excellent ChEs inhibitor, but also as a good modulator on protein expression of AChE, p53, Bax, Bcl-2, LC3, p62, and ULK, indicating its functions against programmed cell apoptosis and decrease of autophagy. 8-7 significantly reversed the glutamate-induced dysfunctions including excessive calcium influx and release from internal organelles, overproduction of nitric oxide (NO) and Aβ high molecular weight oligomer. This compound can penetrate blood-brain barrier (BBB). The in vivo hepatotoxicity assay indicated that 8-7 was much less toxic than tacrine. Altogether, these data strongly support that 8-7 is a potential multitarget-directed ligand (MTDL) for treating Alzheimer's disease (AD).
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http://dx.doi.org/10.1016/j.ejmech.2020.113067DOI Listing
February 2021

A diet rich in fruit and whole grains is associated with a low risk of type 2 diabetes mellitus: findings from a case-control study in South China.

Public Health Nutr 2020 Dec 15:1-12. Epub 2020 Dec 15.

Department of Clinical Nutrition, The First Affiliated Hospital of Sun Yat-sen University, 58 # Zhongshan Road 2, Guangzhou 510080, Guangzhou, China.

Objective: Various foods are associated with or protect against type 2 diabetes mellitus (T2DM). This study was to examine the associations of foods and food patterns with the risk of T2DM in South China.

Design: Case-control study.

Setting: The dietary patterns were identified by a principal components factor analysis. Univariable and multivariable conditional logistic regression analyses were used to analyse the associations between food groups and dietary patterns and the risk of T2DM.

Participants: A total of 384 patients with T2DM and 768 controls.

Results: After adjustment for total energy intake, the standard intake of grains (228·3 ± 71·9 v. 238·8 ± 73·1 g/d, P = 0·025) and fruits (109 ± 90 v. 145 ± 108 g/d, P < 0·001) were lower in T2DM than in controls. Four dietary patterns were identified: (1) high light-coloured vegetables and low grains, (2) high fruits, (3) high red meat and low grains and (4) high dark-coloured vegetable. After adjustment for covariables, multivariable conditional logistic regression analyses showed significant dose-dependent inverse associations between total fruit intake, whole grains intake and the score of the high-fruit dietary pattern (all Pfor trend < 0·001) and the risk of T2DM. The adjusted OR (95 % CI) for T2DM comparing the extreme quartiles were 0·46 (0·29, 0·76) for total fruits, 0·48(0·31, 0·77) for whole grains and 0·42 (0·26, 0·68) for the high-fruit dietary pattern, respectively. Similar associations were observed for all subgroups of fruits (dark-colour and light-colour).

Conclusion: In South China, a diet rich in fruit and whole grains is associated with lower risk of T2DM.
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http://dx.doi.org/10.1017/S1368980020004930DOI Listing
December 2020

Forty-eight weeks of statin therapy for type 2 diabetes mellitus patients with lower extremity atherosclerotic disease: Comparison of the effects of pitavastatin and atorvastatin on lower femoral total plaque areas.

J Diabetes Investig 2021 Jul 30;12(7):1278-1286. Epub 2020 Dec 30.

Department of Endocrinology and Metabolism, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.

Aims/introduction: Type 2 diabetes mellitus is correlated with systemic atherosclerosis. Statin therapies have been proved to reduce low-density lipoprotein cholesterol (LDL-C) level, protecting type 2 diabetes mellitus patients from cardiovascular events. Recently, more interest has been focused on the regression of lower extremity atherosclerotic disease (LEAD) for the potential prevention of amputation. However, the effects of pitavastatin and atorvastatin on LEAD in type 2 diabetes mellitus patients have not been directly compared.

Materials And Methods: This study compared the effects of pitavastatin and atorvastatin on femoral total plaque areas (FTPA), and lipids and glucose metabolism in type 2 diabetes mellitus patients with elevated LDL-C level and LEAD. Type 2 diabetes mellitus patients with LDL-C level >2.6 mmol/L and LEAD were randomly assigned to receive either pitavastatin 2 mg/day or atorvastatin 10 mg/day for 48 weeks. FTPA were measured at baseline and the end of the study. Levels of glucose and lipids profile were measured periodically. The efficacy was evaluated in 63 patients.

Results: The percentage change in FTPA measurements was similar between the pitavastatin group and atorvastatin group (-17.79 ± 21.27% vs -14.34 ± 16.33%), as were the changes in LDL-C (-44.0 ± 18.0% vs -40.3 ± 18.2%) and triglyceride (17.6 ± 20.0% vs 16.2 ± 17.0%). However, the level of high-density lipoprotein cholesterol was significantly higher in the pitavastatin group compared with the atorvastatin group after 48 weeks of treatment (12.9 ± 10.3% vs 7.2 ± 11.7%, P < 0.05). There were no significant differences between groups for the measurements of glucose metabolism.

Conclusion: In type 2 diabetes mellitus patients with elevated LDL-C level and LEAD, 48 weeks of treatment with either pitavastatin or atorvastatin was associated with significant regression of FTPA. Pitavastatin treatment resulted in a significantly higher high-density lipoprotein cholesterol level compared with atorvastatin treatment.
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http://dx.doi.org/10.1111/jdi.13472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264389PMC
July 2021

Genetic alterations in cfDNA of benign and malignant thyroid nodules based on amplicon-based next-generation sequencing.

Ann Transl Med 2020 Oct;8(19):1225

Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: Circulating cell-free DNA (cfDNA) serves as a biomarker in multiple malignant diseases. However, controversy still surrounds the role of cfDNA detection in the diagnosis and monitoring of papillary thyroid carcinoma (PTC). This study set out to identify the role of cfDNA detection in distinguishing between benign and malignant thyroid nodules.

Methods: Tissue, blood cell, and plasma samples were collected from 10 patients with benign nodules and 10 patients with malignant nodules. The DNA isolated from these samples was subject to PCR-based amplification using primers designed for 50 proto-oncogenes and tumor suppressor genes. PCR products were sequenced using Illumina technology, and the mutations were detected with varScan among sequencing data for each sample and comparative analysis was carried out.

Results: Through amplicon sequencing, we found one non-synonymous somatic mutation in the benign nodules and three in the malignant nodules. Among these four mutations, BRAF mutation was detected in the tissue samples of 8 out of the 10 PTC patients, but it was not detected in the benign nodules. However, no BRAF mutation was detected in cfDNA. Further differential analysis of cfDNA indicated that some genes had more mutations in benign patients than in malignant patients, such as MET and IDH, and some genes had more mutations in malignant patients, such as PIK3CA and EZH2.

Conclusions: We found that BRAF mutation was a credible disease-related mutation in PTC; however, it could not be detected in cfDNA. Moreover, there was a large difference in mutation gene distribution between benign and malignant thyroid nodules.
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http://dx.doi.org/10.21037/atm-20-4544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607131PMC
October 2020

Early postpartum dyslipidemia and its potential predictors during pregnancy in women with a history of gestational diabetes mellitus.

Lipids Health Dis 2020 Oct 10;19(1):220. Epub 2020 Oct 10.

Department of Endocrinology, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Rd, Guangzhou, 510080, China.

Background: This study aimed to analyze the incidence of early postpartum dyslipidemia and its potential predictors in women with a history of gestational diabetes mellitus (GDM).

Methods: This was a retrospective study. Five hundred eighty-nine women diagnosed with GDM were enrolled and followed up at 6-12 weeks after delivery. A 75 g oral glucose tolerance test (OGTT) and lipid levels were performed during mid-trimester and the early postpartum period. Participants were divided into the normal lipid group and dyslipidemia group according to postpartum lipid levels. Demographic and metabolic parameters were analyzed. Multiple logistic regression was performed to analyze the potential predictors for early postpartum dyslipidemia. A receiver operating characteristic curve (ROC) was calculated to determine the cut-off values.

Results: A total of 38.5% of the 589 women developed dyslipidemia in early postpartum and 60% of them had normal glucose metabolism. Delivery age, systolic blood pressure (SBP), glycated hemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDL-C) were independent predictors of early postpartum dyslipidemia in women with a history of GDM. The cut-offs of maternal age, SBP, HbA1c values, and LDL-C levels were 35 years, 123 mmHg, 5.1%, and 3.56 mmol/L, respectively. LDL-C achieved a balanced mix of high sensitivity (63.9%) and specificity (69.2%), with the highest area under the receiver operating characteristic curve (AUC) (0.696). When LDL-C was combined with age, SBP, and HbA1c, the AUC reached to 0.733.

Conclusions: A lipid metabolism evaluation should be recommended in women with a history of GDM after delivery, particularly those with a maternal age > 35 years, SBP > 123 mmHg before labor, HbA1c value > 5.1%, or LDL-C levels > 3.56 mmol/L in the second trimester of pregnancy.
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http://dx.doi.org/10.1186/s12944-020-01398-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547505PMC
October 2020
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