Publications by authors named "Jianping Weng"

175 Publications

Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies.

Pharmacol Rev 2021 07;73(3):924-967

Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China (S.X., I.I., X.Z., S.L., J.W.); Sunshine Coast Health Institute, University of the Sunshine Coast, Birtinya, Australia (P.J.L.); School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Woolloongabba, Queensland, Australia (P.J.L., D.K.); Department of Medical Biotechnology, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China (H.L.); The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China (H.L.); Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, National and Local United Engineering Laboratory of Druggability and New Drugs Evaluation, Guangzhou, China (Z.L., P.L.); College of Life Sciences, Key Laboratory of Bioactive Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China (J.H.); Department of Bioengineering, Northeastern University, Boston, Massachusetts (I.C.H., E.E.E.); Department of Chemical Engineering, Northeastern University, Boston, Massachusetts (E.E.E.); Department of Neuroscience, Albert Einstein College of Medicine, New York, New York (E.E.E.); Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio (S.J.C.); and ARC Centre for Personalised Therapeutics Technologies, Department of Biochemistry and Pharmacology, School of Biomedical Science, University of Melbourne, Parkville, Victoria, Australia (A.G.S.)

The endothelium, a cellular monolayer lining the blood vessel wall, plays a critical role in maintaining multiorgan health and homeostasis. Endothelial functions in health include dynamic maintenance of vascular tone, angiogenesis, hemostasis, and the provision of an antioxidant, anti-inflammatory, and antithrombotic interface. Dysfunction of the vascular endothelium presents with impaired endothelium-dependent vasodilation, heightened oxidative stress, chronic inflammation, leukocyte adhesion and hyperpermeability, and endothelial cell senescence. Recent studies have implicated altered endothelial cell metabolism and endothelial-to-mesenchymal transition as new features of endothelial dysfunction. Endothelial dysfunction is regarded as a hallmark of many diverse human panvascular diseases, including atherosclerosis, hypertension, and diabetes. Endothelial dysfunction has also been implicated in severe coronavirus disease 2019. Many clinically used pharmacotherapies, ranging from traditional lipid-lowering drugs, antihypertensive drugs, and antidiabetic drugs to proprotein convertase subtilisin/kexin type 9 inhibitors and interleukin 1 monoclonal antibodies, counter endothelial dysfunction as part of their clinical benefits. The regulation of endothelial dysfunction by noncoding RNAs has provided novel insights into these newly described regulators of endothelial dysfunction, thus yielding potential new therapeutic approaches. Altogether, a better understanding of the versatile (dys)functions of endothelial cells will not only deepen our comprehension of human diseases but also accelerate effective therapeutic drug discovery. In this review, we provide a timely overview of the multiple layers of endothelial function, describe the consequences and mechanisms of endothelial dysfunction, and identify pathways to effective targeted therapies. SIGNIFICANCE STATEMENT: The endothelium was initially considered to be a semipermeable biomechanical barrier and gatekeeper of vascular health. In recent decades, a deepened understanding of the biological functions of the endothelium has led to its recognition as a ubiquitous tissue regulating vascular tone, cell behavior, innate immunity, cell-cell interactions, and cell metabolism in the vessel wall. Endothelial dysfunction is the hallmark of cardiovascular, metabolic, and emerging infectious diseases. Pharmacotherapies targeting endothelial dysfunction have potential for treatment of cardiovascular and many other diseases.
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http://dx.doi.org/10.1124/pharmrev.120.000096DOI Listing
July 2021

Targeting angiopoietin-like 3 (ANGPTL3) in atherosclerosis: from bench to bedside.

Diabetes Obes Metab 2021 May 28. Epub 2021 May 28.

Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Atherosclerotic cardiovascular disease (ASCVD) is the largest cause of morbidity and mortality worldwide. Lipid-lowering therapies are the current major cornerstone of ASCVD management. Statins, ezetimibe, fibrates, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors effectively reduce plasma low-density lipoprotein cholesterol (LDL-C) level in most individuals at risk of atherosclerosis. Still, some patients (such as those with homozygous familial hypercholesterolemia), who did not respond to standard therapies, and some patients who cannot take these agents remain at a high risk of ASCVD. Recent years have witnessed tremendous progress in understanding the mechanism and efficacy of lipid-lowering strategies. Apart from the recently approved PCSK9 and ATP citrate lyase (ACLY) inhibitors, angiopoietin-like 3 (ANGPTL3) is another potential target for the treatment of dyslipidemia and its clinical sequalae-atherosclerosis. ANGPTL3 is a pivotal modulator of plasma triglycerides (TG), LDL-C, and high-density lipoprotein cholesterol (HDL-C) levels achieved by inhibiting the activities of lipoprotein lipase (LPL) and endothelial lipase (EL). Familial combined hypolipidemia is derived from the ANGPTL3 loss-of-function (LOF) mutations, which leads to low levels of LDL-C, HDL-C, and TG and has a 34 percent decreased risk of ASCVD compared with non-carriers. To date, monoclonal antibodies (evinacumab) and antisense oligonucleotides against ANGPTL3 have been investigated in clinical trials for dyslipidemia therapy. Herein, we reviewed the biology and function of ANGPTL3, as well as the latest developments of ANGPTL3 targeted therapies. We also summarized evidence from basic research to clinical trials, with an aim to provide novel insights into biological functions of ANGPTL3 and related targeted therapies. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/dom.14450DOI Listing
May 2021

HLA class I genes modulate disease risk and age at onset together with DR-DQ in Chinese patients with insulin-requiring type 1 diabetes.

Diabetologia 2021 May 22. Epub 2021 May 22.

Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Aims/hypothesis: The study aimed to investigate the effects of HLA class I genes on susceptibility to type 1 diabetes with different onset ages, in addition to the well-established effects of HLA class II genes.

Methods: A total of 361 patients with type 1 diabetes (192 patients with onset <18 years and 169 patients with onset ≥18 years) and 500 healthy control participants from China were enrolled and genotyped for the HLA-A, -B, -C, -DQA1, -DQB1 and -DRB1 genes using next-generation sequencing.

Results: The susceptible DR3 (β = -0.09, p = 0.0009) and DR4-DQ8 (β = -0.13, p = 0.0059) haplotypes were negatively associated with onset age, while the protective DR11 (β = 0.21, p = 0.0314) and DR12 (β = 0.27, p < 0.0001) haplotypes were positively associated with onset age. After adjustment for linkage disequilibrium with DR-DQ haplotypes, A*11:01:01 was positively associated with onset age (β = 0.06, p = 0.0370), while the susceptible C*15:02:01 was negatively associated with onset age (β = -0.21, p = 0.0050). The unit for β was double square-root (fourth root) transformed years of change in onset age associated with per copy of the HLA haplotype/allele. In addition, B*46:01:01 was protective (OR 0.41, 0.46; pc [corrected for multiple comparisons] = 0.0044, 0.0040), whereas A*24:02:01 (OR 2.71, 2.25; pc = 0.0003, 0.0002) and B*54:01:01 (OR 3.96, 3.79; pc = 0.0018, 0.0004) were predisposing in both the <18 group and the ≥18 group compared with healthy control participants. In the context of DR4-DQ4, A*11:01:01 (61.29% vs 28.26%, pc = 0.0144) was increased while the predisposing A*24:02:01 (19.35% vs 47.83%, pc = 0.0403) was decreased in patients with onset ≥18 years when compared with patients with onset <18 years.

Conclusions/interpretation: In addition to DR-DQ haplotypes, novel HLA class I alleles were detected to play a role in susceptibility to type 1 diabetes with different onset ages, which could improve the understanding of disease heterogeneity and has implications for the design of future studies.
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http://dx.doi.org/10.1007/s00125-021-05476-6DOI Listing
May 2021

A bibliometric study of COVID-19 research in Web of Science.

Pharmacol Res 2021 May 9;169:105664. Epub 2021 May 9.

Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China. Electronic address:

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http://dx.doi.org/10.1016/j.phrs.2021.105664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106965PMC
May 2021

Effects of Shuanghuanglian oral liquids on patients with COVID-19: a randomized, open-label, parallel-controlled, multicenter clinical trial.

Front Med 2021 Apr 28. Epub 2021 Apr 28.

Division of Cardiology, Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.
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http://dx.doi.org/10.1007/s11684-021-0853-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079840PMC
April 2021

Three-month outcomes of recovered COVID-19 patients: prospective observational study.

Ther Adv Respir Dis 2021 Jan-Dec;15:17534666211009410

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Room 302, Building 9, 17 Lujiang Road, Luyang District, Hefei, Anhui, 230001, China.

Aims: A novel coronavirus SARS-CoV-2 has resulted in an ongoing global pandemic of Coronavirus disease 2019 (COVID-19). However, the outcomes of recovered patients have not been well defined.

Methods: This is a prospective observational follow-up study of survivors with COVID-19 from a designated tertiary center in Hefei, China. We examined chest computed tomography (CT) scanning, pulmonary function, 6-min walk distance (6MWD), and 36 item Short Form General Health Survey (SF-36).

Results: Among 81 enrolled patients, 62 (77%) patients and 61 (75%) patients, respectively, completed 1-month and 3-month follow-ups. Abnormal CT findings were still present in 73% of patients at 1 month and 54% at 3 months, whereas chest CT scan scores improved progressively at 1-month (5.0 ± 5.1) and 3-month follow up (3.0 ± 4.5) compared with that during hospitalization (11 ± 6.8). Mild restrictive pulmonary impairment was detected in 11% and 10% of patients at 1-month and 3-month follow up, respectively. The 6MWD was 523 ± 77 m in male patients and 484 ± 58 m in female patients, which was significantly lower than in healthy controls (606 ± 68 m, 568 ± 78 m,  < 0.001). SF-36 scores were significantly impaired in the domains of role physical (RP), role emotional (RE), and social functioning (SF) compared with the normal age-matched population. RP was improved at 3-month compared with 1-month follow up in the 41-64 years group ( < 0.01). Multivariable analysis showed that older age (over 40 years) and steroid administration during hospitalization were independently associated with worse chest CT scores at 3-month follow up.

Conclusions: At 3 months, chest CT abnormalities were present in one half of COVID-19 survivors and worse chest CT scores were independently associated with older age and steroid administration during hospitalization. Residual pulmonary function impairments were modest, whereas exercise capacity and SF-36 scores were significantly lower than the general population. Support program and further follow-up evaluations may be needed.
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http://dx.doi.org/10.1177/17534666211009410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064514PMC
May 2021

Current practice and perspectives of healthcare providers regarding preconception care for women with type 1 diabetes in China.

Diabetes Metab Res Rev 2021 May 13;37(4):e3454. Epub 2021 Apr 13.

Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Aims: We aimed to investigate the current practice and perspectives of healthcare providers (HCPs) regarding preconception care (PCC) for women with type 1 diabetes (T1D) in China.

Materials And Methods: A questionnaire based on in-depth interviews with HCPs involved in PCC was released online and advertised via doctor unions in China. The data were categorical variables and were analysed by multivariable logistic regression, Chi-square test, or Wilcoxon rank-sum test.

Results: From November 2016 to January 2017, 992 responses from 31 provinces of China were received (77.3% doctors and 22.7% nurses). Regarding the current status of PCC for T1D, 62.5% of HCPs treated ≤1 woman with T1D monthly on average. Only 16.5% thought they provided proper PCC, and 29.6% reported having sufficient knowledge. Regarding attitudes towards pregnancy with T1D, 92.2% were in favour of women with T1D getting pregnant after proper glycaemic control, and 94.7% perceived their worries regarding pregnancy. Regarding doctor-patient communication, 56.6% spent <10 min per visit, while 58.3% thought ≥20 min was required for adequate communication. HCPs emphasised the importance of multidisciplinary PCC, professional training, and social support. PCC practice was associated with hospital level (OR = 2.450, 95%CI: 1.580-3.799, p < 0.001), HCPs' experience of treating women with T1D (OR = 2.196, 95%CI: 1.516-3.180, p < 0.001), and their communication sufficiency (OR = 3.706, 95%CI: 2.550-5.387, p < 0.001).

Conclusions: The current PCC practice for T1D in China was suboptimal and it was associated with hospital level, HCPs' experience and communication. It is necessary to reinforce professional training and appeal for social resources to improve PCC.
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http://dx.doi.org/10.1002/dmrr.3454DOI Listing
May 2021

Henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.

Diabetes Obes Metab 2021 Mar 26. Epub 2021 Mar 26.

Jiangsu Hengrui Medicine Co., Ltd, Shanghai, China.

Aim: To evaluate the efficacy and safety of henagliflozin in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin.

Material And Methods: This multicentre phase 3 trial included a 24-week randomized, double-blind, placebo-controlled period, followed by a 28-week extension period. Patients with a glycated haemoglobin (HbA1c) level of 7.0% (53 mmol/mol) to 10.5% (91 mmol/mol) were randomized and treated with once-daily placebo (n = 161), henagliflozin 5 mg (n = 162), or henagliflozin 10 mg (n = 160). After 24 weeks, patients on placebo were switched to 5 mg or 10 mg henagliflozin for the additional 28-week treatment, and patients on henagliflozin during 24-week treatment period maintained this initial therapy. The primary endpoint was change in HbA1c from baseline to Week 24.

Results: At Week 24, the least squares mean HbA1c changes versus placebo from baseline were - 0.76% (-8.3 mmol/mol) and - 0.80% (-8.7 mmol/mol) for henagliflozin 5 and 10 mg, respectively (all P < 0.0001). Compared with the placebo group, both doses of henagliflozin lowered fasting plasma glucose, 2-hour postprandial plasma glucose, body weight and blood pressure, and increased the proportions of patients achieving HbA1c <7.0% (53 mmol/mol) at Week 24. The trends in these improvements were sustained over an additional 28 weeks. Slightly higher proportions of ketosis and presence of urine ketone bodies were observed in patients treated with henagliflozin compared to placebo at Week 24. No diabetic ketoacidosis or episodes of severe hypoglycaemia were reported.

Conclusions: Henagliflozin 5 mg or 10 mg as add-on therapy to metformin provided a new therapeutic option for the treatment of T2DM patients who have inadequate glycaemic control with metformin alone, and was generally well tolerated.
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http://dx.doi.org/10.1111/dom.14389DOI Listing
March 2021

Impact of sodium glucose cotransporter 2 (SGLT2) inhibitors on atherosclerosis: from pharmacology to pre-clinical and clinical therapeutics.

Theranostics 2021 4;11(9):4502-4515. Epub 2021 Mar 4.

Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are new oral drugs for the therapy of patients with type 2 diabetes mellitus (T2DM). Research in the past decade has shown that drugs of the SGLT2i class, such as empagliflozin, canagliflozin, and dapagliflozin, have pleiotropic effects in preventing cardiovascular diseases beyond their favorable impact on hyperglycemia. Of clinical relevance, recent landmark cardiovascular outcome trials have demonstrated that SGLT2i reduce major adverse cardiovascular events, hospitalization for heart failure, and cardiovascular death in T2DM patients with/without cardiovascular diseases (including atherosclerotic cardiovascular diseases and various types of heart failure). The major pharmacological action of SGLT2i is through inhibiting glucose re-absorption in the kidney and thus promoting glucose excretion. Studies in experimental models of atherosclerosis have shown that SGLT2i ameliorate the progression of atherosclerosis by mechanisms including inhibition of vascular inflammation, reduction in oxidative stress, reversing endothelial dysfunction, reducing foam cell formation and preventing platelet activation. Here, we summarize the anti-atherosclerotic actions and mechanisms of action of SGLT2i, with an aim to emphasize the clinical utility of this class of agents in preventing the insidious cardiovascular complications accompanying diabetes.
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http://dx.doi.org/10.7150/thno.54498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977463PMC
March 2021

Effectiveness of a WeChat Combined Continuous Flash Glucose Monitoring System on Glycemic Control in Juvenile Type 1 Diabetes Mellitus Management: Randomized Controlled Trial.

Diabetes Metab Syndr Obes 2021 9;14:1085-1094. Epub 2021 Mar 9.

Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, 200233, People's Republic of China.

Purpose: Smartphones have received increasing attention and achieved positive outcomes in diabetes intervention. The widespread use of WeChat in China provides an opportunity for self-management practices in patients with diabetes. Nevertheless, how to combine the strengths of the WeChat platform with traditional medical strategy remains to be explored. This study aimed to evaluate the efficacy of a novel flash glucose monitoring device combined with the WeChat platform in juvenile type 1 diabetes management.

Patients And Methods: A total of 60 juvenile patients with type 1 diabetes were randomly assigned into three groups: a blood glucose self-monitoring group (group A), a flash glucose monitoring (group B), and a flash glucose monitoring combined WeChat-interactive management group (group C). The intergroup differences in demographics, biochemical indicators, and questionnaire scores of the Diabetes Monitoring and Treatment Satisfaction Questionnaire and Diabetes Specific Quality of Life assessment were compared at the baseline and after 6 months.

Results: After the 6-month intervention, groups B and C showed significantly lower glycated hemoglobin A1c (HbA1c) levels compared to those observed at baseline (both <0.05), with the largest decrease observed in group C (group B vs group C, =0.04). Hypoglycemic episodes per month decreased from baseline in groups B and C (both P <0.05) and were more significant in group C ( <0.001). In addition, the DMTSQ scores increased in the 6th month in all groups (all <0.05), and the largest rise in scores was found in group C, followed by groups B and A. The DQOL scores in groups B and C decreased significantly from the baseline (both <0.05), with no change in group A.

Conclusion: Flash glucose monitoring combined with the WeChat-interactive system may help achieve sustained glycemic control and higher satisfaction in patients with juvenile type 1 diabetes.

Trial Registration: This study was registered at chictr.org.cn, number ChiCTR1900025495. Registered 29 August 2019.
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http://dx.doi.org/10.2147/DMSO.S299070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955684PMC
March 2021

Association of Implementation of a Comprehensive Preconception-to-Pregnancy Management Plan With Pregnancy Outcomes Among Chinese Pregnant Women With Type 1 Diabetes: The CARNATION Study.

Diabetes Care 2021 Apr 24;44(4):883-892. Epub 2021 Feb 24.

Faculty of Medicine, Imperial College London, London, U.K.

Objective: To investigate the effect on pregnancy outcome of integrating a comprehensive management plan for patients with type 1 diabetes (T1D) into the World Health Organization universal maternal care infrastructure.

Research Design And Methods: A comprehensive preconception-to-pregnancy management plan for women with T1D was implemented in 11 centers from 8 Chinese cities from 2015 to 2017. Sequential eligible pregnant women ( = 133 out of 137 initially enrolled) with T1D and singleton pregnancies attending these management centers formed the prospective cohort. The main outcome was severe adverse pregnancy outcome comprising maternal mortality, neonatal death, congenital malformations, miscarriage in the second trimester, and stillbirth. We compared pregnancy outcomes in this prospective cohort with two control groups with the same inclusion and exclusion criteria: a retrospective cohort ( = 153) of all eligible pregnant women with T1D attending the same management centers from 2012 to 2014 and a comparison cohort ( = 116) of all eligible pregnant women with T1D receiving routine care from 2015 to 2017 in 11 different centers from 7 cities.

Results: The rate of severe adverse pregnancy outcome was lower in the prospective cohort (6.02%) than in either the retrospective cohort (18.30%; adjusted odds ratio [aOR] 0.31 [95% CI 0.13-0.74]) or the contemporaneous comparison cohort (25.00%; aOR 0.22 [95% CI 0.09-0.52]).

Conclusions: The substantial improvements in the prospective cohort are evidence of a potentially clinically important effect of the comprehensive management plan on pregnancy outcomes among Chinese pregnant women with pregestational T1D. This supports the development of similar approaches in other countries.
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http://dx.doi.org/10.2337/dc20-2692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985418PMC
April 2021

Clinical outcomes of different therapeutic options for COVID-19 in two Chinese case cohorts: A propensity-score analysis.

EClinicalMedicine 2021 Feb 13;32:100743. Epub 2021 Feb 13.

WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Background: The timing of administration of agents and use of combination treatments in COVID-19 remain unclear. We assessed the effectiveness of therapeutics in cohorts in Hong Kong SAR and Anhui, China.

Methods: We conducted propensity-score analysis of 4771 symptomatic patients from Hong Kong between 21st January and 6th December 2020, and 648 symptomatic patients from Anhui between 1st January and 27th February 2020. We censored all observations as at 13st December 2020. Time from hospital admission to discharge, and composite outcome of death, invasive mechanical ventilation or intensive care unit admission across 1) all therapeutic options including lopinavir-ritonavir, ribavirin, umifenovir, interferon-alpha-2b, interferon-beta-1b, corticosteroids, antibiotics, and Chinese medicines, and 2) four interferon-beta-1b combination treatment groups were investigated.

Findings: Interferon-beta-1b was associated with an improved composite outcome (OR=0.55, 95%CI 0.38, 0.80) and earlier discharge (-8.8 days, 95%CI -9.7, -7.9) compared to those not administered interferon-beta-1b. Oral ribavirin initiated within 7 days from onset was associated with lower risk of the composite outcome in Hong Kong (OR=0.51, 95%CI 0.29, 0.90). Lopinavir-ritonavir, intravenous ribavirin, umifenovir, corticosteroids, interferon-alpha-2b, antibiotics or Chinese medicines failed to show consistent clinical benefit. Interferon-beta-1b co-administered with ribavirin was associated with improved composite outcome (OR=0.50, 95%CI 0.32, 0.78) and earlier discharge (-2.35 days, 95%CI -3.65, -1.06) compared to interferon-beta-1b monotherapy.

Interpretation: Our findings support the early administration of interferon-beta-1b alone or in combination with oral ribavirin for COVID-19 patients.

Funding: Hong Kong Health and Medical Research Fund; Hong Kong Innovation and Technology Commission; Chinese Fundamental Research Funds for the Central Universities.
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http://dx.doi.org/10.1016/j.eclinm.2021.100743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881744PMC
February 2021

Glycemic control in children and teenagers with type 1 diabetes around lockdown for COVID-19: A continuous glucose monitoring-based observational study.

J Diabetes Investig 2021 Feb 4. Epub 2021 Feb 4.

Department of Endocrinology and Metabolic Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Aims/introduction: The coronavirus disease 2019 (COVID-19) pandemic urged authorities to impose rigorous quarantines and brought considerable changes to people's lifestyles. The impact of these changes on glycemic control has remained unclear, especially the long-term effect. We aimed to investigate the impact of COVID-19 lockdown on glycemic control in children and adolescents with type 1 diabetes.

Materials And Methods: This observational study enrolled children with type 1 diabetes using continuous glucose monitoring. Continuous glucose monitoring data were extracted from the cloud-based platform before, during and after lockdown. Demographics and lifestyle change-related information were collected from the database or questionnaires. We compared these data before, during and after lockdown.

Results: A total of 43 children with type 1 diabetes were recruited (20 girls; mean age 7.45 years; median diabetes duration 1.05 years). We collected 41,784 h of continuous glucose monitoring data. Although time in range (3.9-10.0 mmol/L) was similar before, during and after lockdown, the median time below range <3.9 mmol/L decreased from 3.70% (interquartile range [IQR] 2.25-9.53%) before lockdown to 2.91% (IQR 1.43-5.95%) during lockdown, but reversed to 4.95% (IQR 2.11-9.42%) after lockdown (P = 0.004). Time below range <3.0 mmol/L was 0.59% (IQR 0.14-2.21%), 0.38% (IQR 0.05-1.35%) and 0.82% (IQR 0.22-1.69%), respectively (P = 0.008). The amelioration of hypoglycemia during lockdown was more prominent among those who had less time spent <3.9 mmol/L at baseline. During lockdown, individuals reduced their physical activity, received longer sleep duration and spent more time on diabetes management. In addition, they attended outpatient clinics less and turned to telemedicine more frequently.

Conclusion: Glycemic control did not deteriorate in children and teenagers with type 1 diabetes around the COVID-19 pandemic. Hypoglycemia declined during lockdown, but reversed after lockdown, and the changes related to lifestyle might not provide a long-term effect.
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http://dx.doi.org/10.1111/jdi.13519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014845PMC
February 2021

Effects of Metformin Added to Insulin in Adolescents with Type 1 Diabetes: An Exploratory Crossover Randomized Trial.

J Diabetes Res 2020 24;2020:7419345. Epub 2020 Dec 24.

Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.

Background: To comprehensively assess the effects of metformin added to insulin on metabolic control, insulin sensitivity, and cardiovascular autonomic function in adolescents with type 1 diabetes.

Materials And Methods: This was an exploratory, crossover, randomized trial conducted in adolescents with type 1 diabetes aged 12-18 years old. Participants were randomly received metformin (≤1000 mg/d) added to insulin for 24 weeks followed by insulin monotherapy for a subsequent 24 weeks or vice versa. Blood pressure, body mass index, insulin dose, estimated insulin sensitivity, glycated hemoglobin A1c (HbA1c), and lipid profiles were measured, with a 72-hour continuous glucose monitoring and 24-hour Holter monitoring performed at baseline, 24, and 50 weeks for the assessments of glucose variability and heart rate variability.

Results: Seventeen patients with mean ± SD age 14.4 ± 2.3 years, body mass index 18.17 ± 1.81 kg/m, median (IQR) diabetes duration 4.50 (3.58, 6.92) years, and HbA1c 9.0% (8.5%, 9.4%) were enrolled. The between-group difference in HbA1c of 0.28% (95% CI -0.39 to 0.95%) was not significant ( = 0.40). Changes in body mass index, insulin dose, blood pressure, lipid profiles, and estimated insulin sensitivity were similar for metformin add-on vs. insulin monotherapy. Glucose variability also did not differ. Compared with insulin monotherapy, metformin add-on significantly increased multiple heart rate variability parameters.

Conclusions: Metformin added to insulin did not improve metabolic control or glucose variability in lean/normal-weight adolescents with type 1 diabetes. However, metformin added to insulin significantly increased heart rate variability, suggesting that metformin might improve cardiovascular autonomic function in this population.
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http://dx.doi.org/10.1155/2020/7419345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785393PMC
December 2020

Association between Urinary Iodine Concentration and Thyroid Nodules in Adults: A Cross-Sectional Study in China.

Biomed Res Int 2020 17;2020:4138657. Epub 2020 Dec 17.

Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Background: Associations between iodine intake and thyroid nodules (TNs) were not consistent. We aimed to illustrate the relationship between urinary iodine concentration (UIC) and TNs.

Methods: A total of 12,698 participants were enrolled in analysis. All of the participants filled out questionnaires and underwent physical examinations, laboratory tests, and thyroid ultrasonography. UIC, serum thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies (TgAb) were measured in the central laboratory.

Results: The prevalence of TNs was 16.00%, and the median UIC was 206.1 g/L. TNs and UIC were negatively related when UIC was less than 527 g/L (adjusted OR = 0.87; 95% CI, 0.80, 0.94), and the relationship between UIC and TNs was not statistically significant when UIC was greater than 527 g/L (adjusted OR = 1.25; 95% CI, 0.98, 1.60). In women, UIC was negatively associated with risk for TNs (adjusted OR 0.95; 95% CI, 0.91, 0.99).

Conclusion: The relationship between TNs and UIC differed between men and women. The risk of TNs decreased with the elevation of UIC in men when UIC was lower than 527 g/L, while UIC and the presence of TNs were negatively correlated in women. In the future, cohort studies or other studies that can explain causality must be conducted to explore the relationship between iodine status and TNs.
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http://dx.doi.org/10.1155/2020/4138657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762642PMC
May 2021

Effects of novel flash glucose monitoring system on glycaemic control in adult patients with type 1 diabetes mellitus: protocol of a multicentre randomised controlled trial.

BMJ Open 2020 12 4;10(12):e039400. Epub 2020 Dec 4.

Department of Endocrinology, the First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, China

Introduction: Optimal glycaemic control is beneficial to prevent and delay microvascular complications in patients with type 1 diabetes mellitus (T1DM). The benefits of flash glucose monitoring (FGM) have been proved among well-controlled adults with T1DM, but evidence for FGM in adults with T1DM who have suboptimal glycaemic control is limited. This study aims to evaluate the effect of FGM in suboptimally controlled adult patients with T1DM .

Methods And Analysis: This open-label, multicentre, randomised trial will be conducted at eight tertiary hospitals and recruit 104 adult participants (≥18 years old) with T1DM diagnosed for at least 1 year and with suboptimal glycaemic control (glycated haemoglobin (HbA1c) ranging from 7.0% to 10.0%). After a run-in period (baseline, 0-2 weeks), eligible participants will be randomised 1:1 to either use FGM or self-monitoring of blood glucose alone consequently for the next 24 weeks. At baseline, 12-14 weeks and 24-26 weeks, retrospective continuous glucose monitoring (CGM) systems will be used in both groups for device-related data collection. Biological metrics, including HbA1c, blood routine, lipid profiles, liver enzymes, questionnaires and adverse events, will be assessed at baseline, week 14 and week 26. All analyses will be conducted on the intent-to-treat population. Efficacy endpoint analyses will also be repeated on the per-protocol population. The primary outcome is the change of HbA1c from baseline to week 26. The secondary outcomes are the changes of CGM metrics, including time spent in range, time spent in target, time spent below range, time spent above range, SD, coefficient of variation, mean amplitude of glucose excursions, high or low blood glucose index, mean of daily differences, percentage of HbA1c in target (<7%), frequency of FGM use, total daily insulin dose and the scores of questionnaires including Diabetes Distress Scale, Hypoglycemia Fear Scale and European Quality of Life Scale.

Ethics And Dissemination: This study was approved by the Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University in January 2017. Ethical approval has been obtained at all centres. All participants will be provided with oral and written information about the trial. The study will be disseminated by peer-review publications and conference presentations.

Trial Registration Number: NCT03522870.
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http://dx.doi.org/10.1136/bmjopen-2020-039400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722373PMC
December 2020

A CRISPR-Cas12a-based specific enhancer for more sensitive detection of SARS-CoV-2 infection.

EBioMedicine 2020 Nov 9;61:103036. Epub 2020 Oct 9.

Medical Research & Laboratory Diagnostic Center, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, China.

Background: Real-time reverse transcription-PCR (rRT-PCR) has been the most effective and widely implemented diagnostic technology since the beginning of the COVID-19 pandemic. However, fuzzy rRT-PCR readouts with high Ct values are frequently encountered, resulting in uncertainty in diagnosis.

Methods: A Specific Enhancer for PCR-amplified Nucleic Acid (SENA) was developed based on the Cas12a trans-cleavage activity, which is specifically triggered by the rRT-PCR amplicons of the SARS-CoV-2 Orf1ab (O) and N fragments. SENA was first characterized to determine its sensitivity and specificity, using a systematic titration experiment with pure SARS-CoV-2 RNA standards, and was then verified in several hospitals, employing a couple of commercial rRT-PCR kits and testing various clinical specimens under different scenarios.

Findings: The ratio (10 min/5 min) of fluorescence change (FC) with mixed SENA reaction (mix-FCratio) was defined for quantitative analysis of target O and N genes, and the Limit of Detection (LoD) of mix-FCratio with 95% confidence interval was 1.2≤1.6≤2.1. Totally, 295 clinical specimens were analyzed, among which 21 uncertain rRT-PCR cases as well as 4 false negative and 2 false positive samples were characterized by SENA and further verified by next-generation sequencing (NGS). The cut-off values for mix-FCratio were determined as 1.145 for positive and 1.068 for negative.

Interpretation: SENA increases both the sensitivity and the specificity of rRT-PCR, solving the uncertainty problem in COVID-19 diagnosis and thus providing a simple and low-cost companion diagnosis for combating the pandemic.

Funding: Detailed funding information is available at the end of the manuscript.
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http://dx.doi.org/10.1016/j.ebiom.2020.103036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544594PMC
November 2020

Elevated fasting blood glucose within the first week of hospitalization was associated with progression to severe illness of COVID-19 in patients with preexisting diabetes: A multicenter observational study.

J Diabetes 2021 Jan 30;13(1):89-93. Epub 2020 Oct 30.

Department of Endocrinology, the First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, China.

Highlights Fasting blood glucose < 10 mmol/L was proposed as a target of glycemic control during the first week of hospitalization in patients with preexisting diabetes. Poor HbA1c levels prior to coronavirus disease 2019 (COVID-19) might not be associated with severity among patients with preexisting diabetes. Mean blood glucose seemed not to be associated with poor prognosis of COVID-19.
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http://dx.doi.org/10.1111/1753-0407.13121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675481PMC
January 2021

Re-detectable positive SARS-CoV-2 RNA tests in patients who recovered from COVID-19 with intestinal infection.

Protein Cell 2021 03 26;12(3):230-235. Epub 2020 Sep 26.

The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

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http://dx.doi.org/10.1007/s13238-020-00778-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518948PMC
March 2021

Use of a do-it-yourself artificial pancreas system is associated with better glucose management and higher quality of life among adults with type 1 diabetes.

Ther Adv Endocrinol Metab 2020 25;11:2042018820950146. Epub 2020 Aug 25.

Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diabetology, Guangzhou 510630, China.

Background: Previous studies show that the use of do-it-yourself artificial pancreas system (DIYAPS) may be associated with better glycemic control characterized by improved estimated hemoglobin A1c (eHbA1c) and time in range among adults with type 1 diabetes (T1D). However, few studies have demonstrated the changes in laboratory-measured HbA1c, which is a more accepted index for glycemic control, after using a DIYAPS.

Methods: This is a retrospective before-after study approaching patients who reported self-use of AndroidAPS. The main inclusion criteria included: T1D; aged ⩾18 years; having complete record of ⩾3 months of continuous AndroidAPS use; with laboratory-measured HbA1c and quality of life scale data before and after 3 months of AndroidAPS use; and not pregnant. The primary outcome was the change in HbA1c between baseline and 3 months after initiation of AndroidAPS use.

Results: Overall, 15 patients (10 females) were included; the median age was 32.2 years (range: 19.2-69.4), median diabetes duration was 9.7 years (range: 1.8-23.7) and median baseline HbA1c was 7.3% (range: 6.4-10.1). The 3 months of AndroidAPS use was associated with substantial reductions in HbA1c [6.79% (SD: 1.29) 7.63% (SD: 1.06),  = 0.002] and glycemic variability when compared with sensor-augmented pump therapy. A lower level of fear of hypoglycemia [22.13 points (SD: 6.87) 26.27 points (SD: 5.82),  = 0.010] was also observed after using AndroidAPS.

Conclusions: The 3 months of AndroidAPS use was associated with significant improvements in glucose management and quality of life among adults with T1D.
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http://dx.doi.org/10.1177/2042018820950146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453453PMC
August 2020

Gender-differential effects on blood glucose levels between acarbose and metformin in Chinese patients with newly diagnosed type 2 diabetes: a sub-analysis of the MARCH trial.

Endocr J 2021 Jan 10;68(1):69-79. Epub 2020 Sep 10.

China-Japan Friendship Hospital, Beijing, 100029, China.

Using the data from the trial of Metformin and AcaRbose in Chinese as the initial Hypoglycemic treatment (MARCH), this study was performed to compare the differential effects of acarbose and metformin on glucose metabolism after stratification by gender. Six hundred and forty patients who had finished the whole 48-week follow-up were included. The reduction of haemoglobin A1c (HbA) was comparable between acarbose- and metformin-treated patients among either females or males, and it was also similar between males and females treated with either acarbose or metformin for 24 and 48 weeks. The dropping of fasting plasma glucose (FPG) in acarbose-treated females was significantly less than that in metformin-treated females at both 24 and 48 weeks. Furthermore, the decrease of 2-hour postprandial glucose (2hPPG) in acarbose-treated males was significantly greater than that in metformin-treated males at both 24 and 48 weeks. Multiple linear regression analysis showed that drug selection was an independent factor affecting the decrease of FPG in female patients while it independently influenced 2hPPG in males at week 24 and 48. The reductions of FPG and 2hPPG at week 24 and 48 were also significantly different between metformin-treated females and metformin-treated males although gender was not an independent regulating factor. Our study indicates that there might be gender-differential effects on FPG and 2hPPG reduction when the comparisons are made between acarbose and metformin treatments.
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http://dx.doi.org/10.1507/endocrj.EJ20-0006DOI Listing
January 2021

Decline of SARS-CoV-2-specific IgG, IgM and IgA in convalescent COVID-19 patients within 100 days after hospital discharge.

Sci China Life Sci 2021 03 28;64(3):482-485. Epub 2020 Aug 28.

The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China.

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http://dx.doi.org/10.1007/s11427-020-1805-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463100PMC
March 2021

Single-cell analysis of two severe COVID-19 patients reveals a monocyte-associated and tocilizumab-responding cytokine storm.

Nat Commun 2020 08 6;11(1):3924. Epub 2020 Aug 6.

Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China.

Several studies show that the immunosuppressive drugs targeting the interleukin-6 (IL-6) receptor, including tocilizumab, ameliorate lethal inflammatory responses in COVID-19 patients infected with SARS-CoV-2. Here, by employing single-cell analysis of the immune cell composition of two severe-stage COVID-19 patients prior to and following tocilizumab-induced remission, we identify a monocyte subpopulation that contributes to the inflammatory cytokine storms. Furthermore, although tocilizumab treatment attenuates the inflammation, immune cells, including plasma B cells and CD8 T cells, still exhibit robust humoral and cellular antiviral immune responses. Thus, in addition to providing a high-dimensional dataset on the immune cell distribution at multiple stages of the COVID-19, our work also provides insights into the therapeutic effects of tocilizumab, and identifies potential target cell populations for treating COVID-19-related cytokine storms.
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http://dx.doi.org/10.1038/s41467-020-17834-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413381PMC
August 2020

Recognition of maturity-onset diabetes of the young in China.

J Diabetes Investig 2021 Apr 9;12(4):501-509. Epub 2020 Sep 9.

Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China.

Aims/introduction: Given that mutations related to maturity-onset diabetes of the young (MODY) are rarely found in Chinese populations, we aim to characterize the mutation spectrum of MODY pedigrees.

Materials And Methods: Maturity-onset diabetes of the young candidate gene- or exome-targeted capture sequencing was carried out in 76 probands from unrelated families fulfilling the clinical diagnostic criteria for MODY. MAF <0.01 in the GnomAD or ExAC database was used to filter significant variants. Sanger sequencing was then carried out to validate findings. Function prediction by SIFT, PolyPhen-2 and PROVEAN or CADD was carried out in missense mutations.

Results: A total of 32 mutations in six genes were identified in 31 families, accounting for 40.79% of the potential MODY families. The MODY subtype detection rate was 18.42% for GCK, 15.79% for HNF1A, 2.63% for HNF4A, and 1.32% for KLF11, PAX4 and NEUROG3. Seven nonsense/frameshift mutations and four missense mutations with damaging prediction were newly identified novel mutations. The clinical features of MODY2, MODY3/1 and MODYX are similar to previous reports. Clinical phenotype of NEUROG3 p.Arg55Glufs*23 is characterized by hyperglycemia and mild intermittent abdominal pain.

Conclusions: This study adds to the emerging pattern of MODY epidemiology that the proportion of MODY explained by known pathogenic genes is higher than that previously reported, and found NEUROG3 as a new causative gene for MODY.
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http://dx.doi.org/10.1111/jdi.13378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015824PMC
April 2021

Targeting inflammation and cytokine storm in COVID-19.

Pharmacol Res 2020 09 27;159:105051. Epub 2020 Jun 27.

Department of Endocrinology, First Affiliated Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, China. Electronic address:

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http://dx.doi.org/10.1016/j.phrs.2020.105051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320704PMC
September 2020

Nanotechnology's application in Type 1 diabetes.

Wiley Interdiscip Rev Nanomed Nanobiotechnol 2020 11 22;12(6):e1645. Epub 2020 May 22.

Department of Endocrinology, The First Affiliated Hospital of USTC, Anhui Provincial Hospital, University of Science and Technology of China, Hefei, China.

Type 1 diabetes mellitus (T1D) is an autoimmune disease caused by the immune system attacking islet cells. T1D, with a long prediabetes period, and the incidence of T1D increases with age during childhood and peaks at 10-14 years. And once it gets overt, it requires lifelong insulin replace treatment. Therefore, the diagnosis of early-stage T1D and effective treatments are important for the management of T1D patients. The imaging methods, such as magnetic resonance imaging (MRI) and so on, were applied in diagnosis of the early stage T1D and its development tracking. The addition of nanomaterials, especially in MRI, can improve the quality of T1D imaging for the diagnosis of T1D at early stage and cause less harm to human body. Meantime, among various treatment options, islet transplantation and immunotherapy are promising, effective, and less independent on insulin. The addition of nanotechnology can effectively reduce the attack of the immune system on drugs and cells, making the therapeutic drug more targeted in the body and prolonging the action time between drugs and cells, thus its addition makes these therapy safer and more efficient. In this review, we attempt to summarize the recent advances in the development of nanotechnology advances of T1D including using nanomaterials for the diagnosis and immunological imaging of T1D, protecting the transplanted islet cells from immune system attack, and delivering relevant molecules to targeted immunocytes. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement.
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http://dx.doi.org/10.1002/wnan.1645DOI Listing
November 2020

Impacts of glycemic variability on the relationship between glucose management indicator from iPro2 and laboratory hemoglobin A1c in adult patients with type 1 diabetes mellitus.

Ther Adv Endocrinol Metab 2020 8;11:2042018820931664. Epub 2020 Jun 8.

Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Department of Endocrinology and Metabolism, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 96 Jinzhai Road, Hefei, China.

Aims: Our aim was to investigate the impact of glycemic variability (GV) on the relationship between glucose management indicator (GMI) and laboratory glycated hemoglobin A1c (HbA1c).

Methods: Adult patients with type 1 diabetes mellitus (T1D) were enrolled from five hospitals in China. All subjects wore the iPro2 system for 14 days before HbA1c was measured at baseline, 3 months and 6 months. Data derived from iPro2 sensor was used to calculate GMI and GV parameters [standard deviation (SD), glucose coefficient of variation (CV), and mean amplitude of glycemic excursions (MAGE)]. Differences between GMI and laboratory HbA1c were assessed by the absolute value of the hemoglobin glycation index (HGI).

Results: A total of 91 sensor data and corresponding laboratory HbA1c, as well as demographic and clinical characteristics were analyzed. GMI and HbA1c were 7.20 ± 0.67% and 7.52 ± 0.73%, respectively. The percentage of subjects with absolute HGI 0 to lower than 0.1% was 21%. GMI was significantly associated with laboratory HbA1c after basic adjustment (standardized β = 0.83,  < 0.001). Further adjustment for SD or MAGE reduced the standardized β for laboratory HbA1c from 0.83 to 0.71 and 0.73, respectively (both  < 0.001). In contrast, the β remained relatively constant when further adjusting for CV. Spearman correlation analysis showed that GMI and laboratory HbA1c were correlated for each quartile of SD and MAGE (all  < 0.05), with the corresponding correlation coefficients decreased across ascending quartiles.

Conclusions: This study validated the GMI formula using the iPro2 sensor in adult patients with T1D. GV influenced the relationship between GMI and laboratory HbA1c.
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http://dx.doi.org/10.1177/2042018820931664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281639PMC
June 2020

COVID-19 and Kawasaki disease in children.

Pharmacol Res 2020 09 25;159:104951. Epub 2020 May 25.

Department of Endocrinology and Metabolism, The First Affiliated Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, 230037, China. Electronic address:

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http://dx.doi.org/10.1016/j.phrs.2020.104951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247462PMC
September 2020

Adult-onset type 1 diabetic patients with less severe clinical manifestation have less risk DR-DQ genotypes than childhood-onset patients.

Diabetes Metab Res Rev 2021 Jan 21;37(1):e3357. Epub 2020 Jun 21.

Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: The aim of this study was to investigate differences in clinical features and HLA genotypes between adult-onset and childhood-onset patients with type 1 diabetes in a Chinese population.

Materials And Methods: This study enrolled 716 Han Chinese patients with type 1 diabetes from Guangdong (258 childhood-onset and 458 adult-onset) to compare their clinical features. Of them 214 patients with classical type 1 diabetes (100 childhood-onset and 114 adult-onset) were selected for HLA DR and DQ genotyping by next-generation sequencing.

Results: Adult-onset patients were characterized by longer duration of symptoms before diagnosis, lower frequency of DKA at disease onset, less frequent autoantibody positivity, higher serum C-peptide concentrations, and better glycemic control. These findings were replicated in the restricted cohort of 214 patients with classical type 1 diabetes. Compared with childhood-onset patients, adult-onset patients had a lower frequency of the DR9 haplotype, as well as lower frequency of high-risk DR3/DR4 and DR3/DR9 genotypes, but higher frequency of DR3/DR3 genotype and DR3/X, DR4/X or DR9/X (X, non-risk) genotypes.

Conclusions: Adult-onset type 1 diabetic patients with susceptible haplotypes (DR3, DR4 or DR9) were more likely to carry protective DR-DQ haplotypes than childhood-onset patients, which suggested the association between less risk DR-DQ genotypes and the less severe clinical manifestation in adult-onset patients.
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http://dx.doi.org/10.1002/dmrr.3357DOI Listing
January 2021

Biochemical characterization of SARS-CoV-2 nucleocapsid protein.

Biochem Biophys Res Commun 2020 06 30;527(3):618-623. Epub 2020 Apr 30.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China; Hefei National Laboratory for Physical Sciences at Microscale, Laboratory of Structural Immunology, CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230027, China; CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Science, Shanghai, 200031, China. Electronic address:

The nucleocapsid (N) protein is an important antigen for coronavirus, which participate in RNA package and virus particle release. In this study, we expressed the N protein of SARS-CoV-2 and characterized its biochemical properties. Static light scattering, size exclusive chromatography, and small-angle X-ray scattering (SAXS) showed that the purified N protein is largely a dimer in solution. CD spectra showed that it has a high percentage of disordered region at room temperature while it was best structured at 55 °C, suggesting its structural dynamics. Fluorescence polarization assay showed it has non-specific nucleic acid binding capability, which raised a concern in using it as a diagnostic marker. Immunoblot assays confirmed the presence of IgA, IgM and IgG antibodies against N antigen in COVID-19 infection patients' sera, proving the importance of this antigen in host immunity and diagnostics.
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http://dx.doi.org/10.1016/j.bbrc.2020.04.136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190499PMC
June 2020