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Background: Both type 1 diabetes mellitus (T1DM) and metabolic syndrome (MetS) are associated with an elevated risk of morbidity and mortality yet with increasing heterogeneity. This study primarily aimed to evaluate the prevalence of MetS among adult patients with T1DM in China and investigate its associated risk factors, and relationship with microvascular complications.Methods: We included adult patients who had been enrolled in the Guangdong T1DM Translational Medicine Study conducted from June 2010 to June 2015. MetS was defined according to the updated National Cholesterol Education Program criterion. Logistic regression models were used to estimate the odds ratio (OR) for the association between MetS and the risk of diabetic kidney disease (DKD) and diabetic retinopathy (DR).Results: Among the 569 eligible patients enrolled, the prevalence of MetS was 15.1%. While female gender, longer diabetes duration, higher body mass index, and glycosylated hemoglobin A1c (HbA1c) were risk factors associated with MetS (OR, 2.86, 1.04, 1.14, and 1.23, respectively), received nutrition therapy education was a protective factor (OR, 0.46). After adjustment for gender, age, diabetes duration, HbA1c, socioeconomic and lifestyle variables, MetS status was associated with an increased risk of DKD and DR (OR, 2.14 and 3.72, respectively; both P

Women with hormone receptor positive breast cancer may receive 5 years of treatment with aromatase inhibitors but the magnitude of benefit was relatively small. Our goal was to develop a tool for identification of women with limited treatment benefit. Regression analyses were applied to women treated by placebo in CCTG MA.17R trial (NCT00754845) to identify important prognostic factors associated with distant recurrence and develop a nomogram for predicting 5-year likelihood of distant recurrence, which was internally validated using bootstrap resampling method. Differential treatment effects between risk categories derived from the nomogram were evaluated among all women enrolled through interaction test between treatment and risk category. A total of 1735 women were included and the final model from 866 women treated by placebo identified the following three factors associate with distant recurrence: tumor size, nodal status, and presence of cardiovascular disease. The nomogram derived from the final model exhibited good discrimination power with a bootstrap-corrected concordance index of 0.71 and, importantly, identified 64% of low risk patients in whom extended treatment has limited benefit. Interaction between treatment and risk category derived from the nomogram was significant (p = 0.04). A nomogram with good performance may be used to accurately predict distant recurrence risk and also benefits with extended treatment after 5 years of aromatase inhibitors. Future independent validation of the proposed nomogram is warranted. NCT00754845

ContextContinuous glucose monitoring (CGM) overcomes the limitations of glycated hemoglobin (HbA1c).ObjectiveThis study aimed to investigate the relationship between CGM metrics and laboratory HbA1c in pregnant women with type 1 diabetes.MethodsAn observational study enrolled pregnant women with type 1 diabetes who wore CGM devices during pregnancy and postpartum from 11 hospitals in China from January 2015 to June 2019. CGM data were collected to calculate time in range (TIR), time above range (TAR), time below range (TBR), and glycemic variability parameters. Relationships between the CGM metrics and HbA1c were explored. Linear and curvilinear regressions were conducted to investigate the best-fitting model to clarify the influence of HbA1c on the TIR-HbA1c relationship during pregnancy.ResultsA total of 272 CGM data and corresponding HbA1c from 98 pregnant women with type 1 diabetes and their clinical characteristics were analyzed in this study. Mean HbA1c and TIR were 6.49 ± 1.29% and 76.16 ± 17.97% during pregnancy, respectively. HbA1c was moderately correlated with TIR3.5-7.8(R = –0.429, P = .001), mean glucose (R = 0.405, P = .001) and TAR7.8 (R = 0.435, P = .001), but was weakly correlated with TBR3.5 (R = 0.034, P = .001) during pregnancy. On average, a 1% (11 mmol/mol) decrease in HbA1c corresponded to an 8.5% increase in TIR3.5–7.8. During pregnancy, HbA1c of 6.0%, 6.5%, and 7.0% were equivalent to a TIR3.5–7.8 of 78%, 74%, and 69%, respectively.ConclusionWe found there was a moderate correlation between HbA1c and TIR3.5–7.8 during pregnancy. To achieve the HbA1c target of less than 6.0%, pregnant women with type 1 diabetes should strive for a TIR3.5–7.8 of greater than 78% (18 hours 43 minutes) during pregnancy.

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.

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 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 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 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 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. Graphical abstract

Objective Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against neuromuscular junctions. Myasthenic crisis (MC) represents the most severe state of MG with high in‐hospital mortality. We aimed to identify immune signatures using in‐depth profiling in MC, and to assess the correlations between immune biomarkers with clinical severity longitudinally. Methods We studied 181 participants including 57 healthy controls, 96 patients with MG who never experienced crisis and 28 MC patients from December 2018 through June 2020. Follow‐up visits occurred prospectively from crisis to 6 months off‐mechanical ventilation. The frequencies of 20 CD4+ T subpopulations and 18 serum cytokines were associated with clinical scores using correlations and principal component analysis. Results Patients in crisis exhibited a proinflammatory CD4+T response with elevated Th1 (P = 0.026), and Th17 cells (P = 0.032); decreased T follicular helper 2 (Tfh2) cells (P

The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological consequences of COVID-19 are limited. To ascertain the consequences of COVID-19 on sperm parameters after recovery, we recruited 41 reproductive-aged male patients who had recovered from COVID-19, and analyzed their semen parameters and serum sex hormones at a median time of 56 days after hospital discharge. For longitudinal analysis, a second sampling was obtained from 22 of the 41 patients after a median time interval of 29 days from first sampling. Compared with controls who had not suffered from COVID-19, the total sperm count, sperm concentration, and percentages of motile and progressively motile spermatozoa in the patients were significantly lower at first sampling, while sperm vitality and morphology were not affected. The total sperm count, sperm concentration, and number of motile spermatozoa per ejaculate were significantly increased and the percentage of morphologically abnormal sperm was reduced at the second sampling compared with those at first in the 22 patients examined. Though there were higher prolactin and lower progesterone levels in patients at first sampling than those in controls, no significant alterations were detected for any sex hormones examined over time following COVID-19 recovery in the 22 patients. Although it should be interpreted carefully, these findings indicate an adverse but potentially reversible consequence of COVID-19 on sperm quality.

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.

As a first-line treatment for diabetes, the insulin-sensitizing biguanide, metformin, regulates glucose levels and positively affects cardiovascular function in patients with diabetes and cardiovascular complications. Endothelial dysfunction (ED) represents the primary pathological change of multiple vascular diseases, because it causes decreased arterial plasticity, increased vascular resistance, reduced tissue perfusion and atherosclerosis. Caused by "biochemical injury", ED is also an independent predictor of cardiovascular events. Accumulating evidence shows that metformin improves ED through liver kinase B1 (LKB1)/5'-adenosine monophosphat-activated protein kinase (AMPK) and AMPK-independent targets, including nuclear factor-kappa B (NF-κB), phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), endothelial nitric oxide synthase (eNOS), sirtuin 1 (SIRT1), forkhead box O1 (FOXO1), krüppel-like factor 4 (KLF4) and krüppel-like factor 2 (KLF2). Evaluating the effects of metformin on endothelial cell functions would facilitate our understanding of the therapeutic potential of metformin in cardiovascular diabetology (including diabetes and its cardiovascular complications). This article reviews the physiological and pathological functions of endothelial cells and the intact endothelium, reviews the latest research of metformin in the treatment of diabetes and related cardiovascular complications, and focuses on the mechanism of action of metformin in regulating endothelial cell functions.

Highlights Fasting blood glucose

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, Flow chart of the procedures for screening of MODY mutations.

BACKGROUND Limited data on the efficacy of the additional metformin therapy in patients with type 1 diabetes mellitus (T1DM) under real-life conditions have been available so far. METHODS Patients aged ≥18 years with a duration of T1DM for at least 1 year were included in this multicenter observational study. Patients with insulin combined with metformin therapy (MET group) were compared with those with insulin therapy only (INS group). RESULTS A total of 76 patients in the MET group were compared with 655 patients in the INS group. At baseline, patients with dyslipidemia were more prevalent in the MET group (17.6% vs 9.0%; P = .006), and they also had a higher body mass index (BMI) (21.7 ± 3.2 kg/m2 vs 20.4 ± 2.6 kg/m2 ; P

BackgroundLung adenocarcinoma (LUAD) is the most common pathological type of lung cancer, with high incidence and mortality. To improve the curative effect and prolong the survival of patients, it is necessary to find new biomarkers to accurately predict the prognosis of patients and explore new strategy to treat high-risk LUAD.MethodsA comprehensive genome-wide profiling analysis was conducted using a retrospective pool of LUAD patient data from the previous datasets of Gene Expression Omnibus (GEO) including GSE18842, GSE19188, GSE40791 and GSE50081 and The Cancer Genome Atlas (TCGA). Differential gene analysis and Cox proportional hazard model were used to identify differentially expressed genes with survival significance as candidate prognostic genes. The Kaplan–Meier with log-rank test was used to assess survival difference. A risk score model was developed and validated using TCGA-LUAD and GSE50081. Additionally, The Connectivity Map (CMAP) was used to predict drugs for the treatment of LUAD. The anti-cancer effect and mechanism of its candidate drugs were studied in LUAD cell lines.ResultsWe identified a 5-gene signature (KIF20A, KLF4, KRT6A, LIFR and RGS13). Risk Score (RS) based on 5-gene signature was significantly associated with overall survival (OS). Nomogram combining RS with clinical pathology parameters could potently predict the prognosis of patients with LUAD. Moreover, gliclazide was identified as a candidate drug for the treatment of high-RS LUAD. Finally, gliclazide was shown to induce cell cycle arrest and apoptosis in LUAD cells possibly by targeting CCNB1, CCNB2, CDK1 and AURKA.ConclusionThis study identified a 5-gene signature that can predict the prognosis of patients with LUAD, and Gliclazide as a potential therapeutic drug for LUAD. It provides a new direction for the prognosis and treatment of patients with LUAD.

We aimed to report pregnancy outcomes of women with type 1 diabetes (T1D) in China, on which data were sparse.This is a nationwide retrospective study conducted in 11 general medical centers in 8 cities across China. We investigated the clinical data of all women who attended these centers with a singleton pregnancy and whose pregnancy ended between 1 January 2004 and 31 December 2014. Pregnancies of women with pregestational T1D were ascertained and compared with those of women without T1D.From over 300 000 pregnancies over the 11-year study period, we identified 265 singleton pregnancies of women with T1D. One maternal death was documented among 265 (0.37%) women with T1D and 83 among 318 486 (0.03%) women without T1D. Women with T1D suffered from higher rates of pregnancy loss (13.21% vs 2.92%, crude risk ratio [cRR] 5.08 [95% CI, 3.56-7.26]) and preeclampsia (17.74% vs 4.20%, cRR 4.94 [95% CI, 3.60-6.77]) compared with those without T1D. Infants of these women with T1D had elevated rates of neonatal death (5.65% vs 0.16%, cRR 37.36 [95% CI, 21.21-65.82]) and congenital malformation(s) (8.26% vs 3.53%, cRR 2.46 [95% CI, 1.54-3.93]) compared with those of women without T1D. No significant improvement in pregnancy outcomes in women with T1D was observed over the period 2004 to 2014.Pregnancy outcomes were persistently poor in women with T1D during 2004 to 2014 in China. Pregnancy care needs to be improved to reduce adverse pregnancy outcomes among Chinese women with T1D.背景: 本研究旨在报道中国1型糖尿病(T1D)患者的妊娠结局，该方面相关研究数据较少。 方法: 对全国8个城市的11家综合医疗中心进行回顾性研究。我们调查了2004年1月1日至2014年12月31日期间所有在这些中心就诊的单胎妊娠妇女的临床资料。确定妊娠期T1D的妇女妊娠情况，并与无T1D的妇女进行比较。 结果: 在11年的研究期间，从超过30万例妊娠中，我们鉴定了265例患有T1D的单胎妊娠妇女。265例T1D孕妇中有一例(0.37%)死亡，318486例无T1D孕妇中有83例(0.03%)死亡。与无T1D的女性相比，T1D的女性流产率更高(13.21% vs 2.92%，粗风险比[cRR] 5.08, 95%置信区间[CI] 3.56-7.26)、子痫前期(17.74% vs 4.20%， cRR 4.94, 95% CI 3.60-6.77)。与未患T1D的妇女相比，患有T1D妇女的婴儿新生儿死亡率(5.65% vs 0.16%， cRR 37.36, 95% CI 21.21-65.82)和先天性畸形率(8.26% vs 3.53%， cRR 2.46, 95% CI 1.54-3.93)较高。在2004-2014年间，T1D患者妊娠结局无明显改善。 结论: 2004-2014年中国T1D患者妊娠结局仍然较差。需要改善妊娠护理以减少中国T1D女性的不良妊娠结局。.

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 1β 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.

Aims: To investigate the relationship between time-in-range (TIR) and laboratory glycated hemoglobin A1c (HbA1c) in pregnant women with type 1 diabetes mellitus (T1DM). Methods: An observational study enrolled pregnant women with T1DM who wore continuous glucose monitoring (CGM) system devices (iProTM2 system) in the first, second, third trimesters and postpartum from 11 hospitals in China from January 2015 to June 2018. Data derived from the CGM system were used to calculate TIR, time above range (TAR), time below range (TBR), mean glucose (MG), and glycemic variability (GV) parameters. Relationships were explored between the CGM metrics and HbA1c. Linear and curvilinear regressions were conducted to investigate the best-fitting model to account for the influence of gestational changes in HbA1c on the TIR- HbA1c relationship. Results: A total of 272 CGM data and corresponding laboratory HbA1c from 98 pregnant women with T1DM, as well as demographic and clinical characteristics were analyzed. Mean HbA1c and TIR were 6.49±1.29% and 76.16±17.97% during pregnancy, respectively. HbA1c was moderately correlated with TIR3.5-7.8(R=-0.429, P=0.001), mean glucose (R= 0.405, P=0.001) and the TAR7.8 (R=0.435, P=0.001), but was weakly correlated with TBR3.5 (R=0.034, P=0.001) during pregnancy. On average, a 1% (11 mmol/mol) difference in HbA1c corresponded to an 8.5% difference in TIR3.5-7.8. During pregnancy, HbA1c of 6%, 6.5% and 7% were equivalent to a TIR3.5-7.8 of 78%, 74%, and 69%, respectively. Conclusions: We found a moderate correlation between HbA1c and TIR3.5-7.8 during pregnancy. To achieve the HbA1c target 78% (18h 43min/per day), during pregnancy. Disclosure P. Ling: None. J. Weng: None. C. Wang: None. D. Yang: None. S. Luo: None. X. Zheng: None. J. Lv: None. J. Yan: None. W. Xu: None. B. Yao: None. Funding National Health and Family Planning Commission of the People’s Republic of China; Foundation for Public Welfare Industry Research Project (201502011); National Key Research and Development Program of China (2017YFC1309600); National Natural Science Foundation of China (81941022)

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, p 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. The reviews of this paper are available via the supplemental material section.

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

Type 2 diabetes mellitus (T2DM) is closely associated with cardiovascular diseases (CVD), including atherosclerosis, hypertension and heart failure. Some anti-diabetic medications are linked with an increased risk of weight gain or hypoglycemia which may reduce the efficacy of the intended anti-hyperglycemic effects of these therapies. The recently developed receptor agonists for glucagon-like peptide-1 (GLP-1RAs), stimulate insulin secretion and reduce glycated hemoglobin levels without having side effects such as weight gain and hypoglycemia. In addition, GLP1-RAs demonstrate numerous cardiovascular protective effects in subjects with or without diabetes. There have been several cardiovascular outcomes trials (CVOTs) involving GLP-1RAs, which have supported the overall cardiovascular benefits of these drugs. GLP1-RAs lower plasma lipid levels and lower blood pressure (BP), both of which contribute to a reduction of atherosclerosis and reduced CVD. GLP-1R is expressed in multiple cardiovascular cell types such as monocyte/macrophages, smooth muscle cells, endothelial cells, and cardiomyocytes. Recent studies have indicated that the protective properties against endothelial dysfunction, anti-inflammatory effects on macrophages and the anti-proliferative action on smooth muscle cells may contribute to atheroprotection through GLP-1R signaling. In the present review, we describe the cardiovascular effects and underlying molecular mechanisms of action of GLP-1RAs in CVOTs, animal models and cultured cells, and address how these findings have transformed our understanding of the pharmacotherapy of T2DM and the prevention of CVD.

Coronavirus disease 2019 (COVID-19) is regarded as an endothelial disease (endothelialitis) with its patho-mechanism being incompletely understood. Emerging evidence has demonstrated that endothelial dysfunction precipitates COVID-19 and its accompanying multi-organ injuries. Thus, pharmacotherapies targeting endothelial dysfunction have potential to ameliorate COVID-19 and its cardiovascular complications. The objective of the present study is to evaluate whether kruppel-like factor 2 (KLF2), a master regulator of vascular homeostasis, represents a therapeutic target for COVID-19-induced endothelial dysfunction. Here, we demonstrate that the expression of KLF2 was reduced and monocyte adhesion was increased in endothelial cells treated with COVID-19 patient serum due to elevated levels of pro-adhesive molecules, ICAM1 and VCAM1. IL-1β and TNF-α, two cytokines elevated in cytokine release syndrome in COVID-19 patients, decreased KLF2 gene expression. Pharmacologic (atorvastatin and tannic acid) and genetic (adenoviral overexpression) approaches to augment KLF2 levels attenuated COVID-19-serum-induced increase in endothelial inflammation and monocyte adhesion. Next-generation RNA-sequencing data showed that atorvastatin treatment leads to a cardiovascular protective transcriptome associated with improved endothelial function (vasodilation, anti-inflammation, antioxidant status, anti-thrombosis/-coagulation, anti-fibrosis, and reduced angiogenesis). Finally, knockdown of KLF2 partially reversed the ameliorative effect of atorvastatin on COVID-19-serum-induced endothelial inflammation and monocyte adhesion. Collectively, the present study implicates loss of KLF2 as an important molecular event in the development of COVID-19-induced vascular disease and suggests that efforts to augment KLF2 levels may be therapeutically beneficial.

Coronavirus disease 2019 (COVID-19) is regarded as an endothelial disease (endothelialitis) with its mechanism being incompletely understood. Emerging evidence has demonstrated that the endothelium represents the Achilles' heel in COVID-19 patients and that endothelial dysfunction precipitates COVID-19 and accompanying multi-organ injuries. Thus, pharmacotherapies targeting endothelial dysfunction have potential to ameliorate COVID-19 and its cardiovascular complications. Primary human umbilical vein endothelial cells (HUVECs) and human pulmonary microvascular endothelial cells (HPMECs) were treated with serum from control subjects or COVID-19 patients. Downstream monocyte adhesion and associated gene/protein expression was evaluated in endothelial cells exposed to COVID-19 patient serum in the presence of KLF2 activator (Atorvastatin) or KLF2 overexpression by an adenoviral vector. Here, we demonstrate that the expression of KLF2 was significantly reduced and monocyte adhesion was increased in endothelial cells treated with COVID-19 patient serum due to elevated levels of pro-adhesive molecules, ICAM1 and VCAM1. IL-1β and TNF-α, two cytokines observed in cytokine release syndrome in COVID-19 patients, decreased KLF2 gene expression. Next-generation RNA-sequencing data showed that atorvastatin treatment leads to a cardiovascular protective transcriptome associated with improved endothelial function (vasodilation, anti-inflammation, antioxidant status, anti-thrombosis/-coagulation, anti-fibrosis and reduced angiogenesis). Treatment of HPMECs with atorvastatin or KLF2 adenovirus ameliorate COVID-19 serum-induced increase in endothelial inflammation and monocyte adhesion by increasing KLF2 expression. Altogether, the present study demonstrates that genetic and pharmacological activation of KLF2 represses COVID-19 associated endothelial dysfunction, heralding a potentially new direction to treat endothelialitis accompanying COVID-19.

Introduction During the Coronavirus Disease 2019 global pandemic, maternal and newborn wellbeing has received much attention. Detailed reports of infected women breastfeeding their infants are uncommon. Due to incomplete information available, full data about those infants’ outcomes are lacking, and evidence of infectivity through breastfeeding has not been documented. Main Issue Here, we report about a mother who breastfed her infant until she was confirmed with the SARS-Cov-2 infection. After follow-up, we have confirmed that the infant, who was breastfed by the infected mother, was not infected. Methods A 33-year-old woman gave birth to a full-term male infant on November 8, 2019. Since birth, she had been exclusively breastfeeding the baby until she was confirmed with the SARS-Cov-2 infection on February 8, 2020. She was hospitalized, isolated from her baby, and stopped breastfeeding. Even though she remained asymptomatic, her milk was expressed using a breast pump and discarded. The mother’s milk sample was collected on February 9, 2020, and the result of the nucleic acid test for COVID-19 was negative. Her infant was asymptomatic and remained virus negative. Her laboratory findings and chest Computed Tomography imaging was normal. She was treated according to the national protocol with aerosolized interferon α2β, lopinavir/ritonavir and ribavirin. Her serum SARS-CoV-2 specific antibodies(IgG and IgM) tested positive when discharged. She returned to breastfeeding after discharge. Conclusion Our findings suggest that breastfeeding may be less of a risk than anticipated. Additional research is needed to explore this possibility.

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.

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, Glycemic control did not deteriorate in type 1 diabetes patients around the COVID‐19 pandemics. There was a small, but significant, improvement in hypoglycemia in people with type 1 diabetes during lockdown for COVID‐19, but such improvement disappeared after lockdown. A stable and relaxed lifestyle might lead to better glycemic control, but lifestyle changes might not provide a long‐term effect.

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 (n = 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 (n = 153) of all eligible pregnant women with T1D attending the same management centers from 2012 to 2014 and a comparison cohort (n = 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.

Monitoring the levels of SARS-CoV-2 specific antibodies such as IgG, M and A in COVID-19 patient is an alternative method for diagnosing SARS-CoV-2 infection and an simple way to monitor immune responses in convalescent patients and after vaccination. Here, we assessed the levels of SARS-CoV-2 RBD specific antibodies in twenty-seven COVID-19 convalescent patients over 28–99 days after hospital discharge. Almost all patient who had severe or moderate COVID-19 symptoms and a high-level of IgG during the hospitalization showed a significant reduction at revisit. The remaining patients who had a low-level IgG during hospitalization stayed low at revisit. As expected, IgM levels in almost all convalescent patients reduced significantly or stayed low at revisit. The RBD-specific IgA levels were also reduced significantly at revisit. We also attempted to estimate decline rates of virus-specific antibodies using a previously established exponential decay model of antibody kinetics after infection. The predicted days when convalescent patients’ RBD-specific IgG reaches to an undetectable level are approximately 273 days after hospital discharge, while the predicted decay times are 150 days and 108 days for IgM and IgA, respectively. This investigation and report will aid current and future studies to develope SARS-CoV-2 vaccines that are potent and long-lasting.

In this population-based study, we identified 307 confirmed COVID-19 cases from massive surveillance, including 129 551 individuals screened at fever clinics or returning from Hubei and 3710 close contacts of confirmed COVID-19 patients. Among them, 17 patients were asymptomatic at initial clinical assessment. These asymptomatic patients on admission accounted for a small proportion of all patients (5.54%) with relatively weak transmissibility, and the detection rate was 0.35 per 100 close contacts. Moreover, the dynamics of symptoms of the 307 patients showed that the interval from symptom remission to the final negativity of viral nucleic acid was 5.0 days (interquartile range 2.0 to 11.0 days), with 14 patients (4.56%) having re-detectable viral RNA after discharge. Overall, our findings suggested asymptomatic carriers and presymptomatic patients only accounted for a small proportion of COVID-19 patients. Also, the asymptomatic phase during recovery from COVID-19 implied that negativity in viral RNA is necessary as a de-isolation criterion and follow-up is recommended.

Limited data on head-to-head comparisons between the flash glucose monitoring (FGM) system (FreeStyle Libre®, FSL) and retrospective continuous glucose monitoring (CGM) system (IproTM2) were available. The study aimed to compare glycemic metrics derived from two devices in adult patients with type 1 diabetes (T1D). Adult T1D patients with HbA1c of 7 to 10% were recruited and randomized to adopt FSL or self-monitoring blood glucose in the 24-week trial (NCT03522870). In the FSL group, glucose was simultaneously measured by FSL and IproTM2s on patients’ different arms for 14 days at 12 and 24 weeks. Data collected on the day of insertion and detachment and those of insufficient quality (0.05). In the 14-days wearing of the different devices simultaneously, there was a close agreement between FSL and Ipro2 but significant differences were observed in TIR and time spent in hypoglycemia. Disclosure Y. Zhou: None. H. Deng: None. D. Yang: None. J. Yan: None. W. Xu: None. H. Liu: None. L. Gan: None. S. Luo: None. X. Zheng: None. H. Liang: None. B. Yao: None. J. Weng: None. Funding National Key Research and Development Program of China (2017YFC1309600); Natural Science Foundation of Guangdong Province (2018A030313251)

Association between HLA class I genes and onset ages of type 1 diabetes (T1D) has been reported in Europeans—risk A*2402 and B*3906 were associated with an earlier age at onset. However, there exists considerable heterogeneity in different populations and individuals of T1D. Its incidence varies dramatically by country and region, ranging from > 60 per 100000 persons years in Finland to 1.01 per 100000 persons years in China. With latter, as many as 65% of the newly diagnosed patients occurred among adults. Furthermore, little is known about the distribution of HLA class I alleles in Chinese patients with T1D at different onset ages. To clarify the contribution of HLA class I genes to T1D with different onset ages in Chinese, 376 patients with T1D and 500 healthy controls were enrolled in this study to analyze HLA-A, B, C alleles conditioning on DRB1-DQA1-DQB1 haplotypes. Among them, 159 patients with an onset age < 15 years were assigned into early-onset group (EG) while the rest 217 patients constituted the late-onset group (LG). After adjustment for linkage disequilibrium with HLA class II, A*24:02:01 (OR 2.7), B*54:01:01 (OR 4.1) and C*15:02:01 (OR 7.8) were associated with susceptibility in EG patients, while A*24:02:01 (OR 2.3), B*15:02:01 (OR 2.5), B*54:01:01 (OR 3.6) and C*08:01:01 (OR 2.0) were predisposing in LG patients when compared with control subjects. Besides, B*46:01:01 (OR 0.4) conferred protection against T1D in EG patients, while B*46:01:01 (OR 0.5) and A*02:07:01 (OR 0.6) were protective in LG patients. When comparing the distribution of HLA class I genes between EG and LG, the data showed that the frequency of A*11:01:01 was higher in LG than EG. When A*11:01:01 was analyzed in patients at all ages using linear regression, it showed a positive correlation between A*11:01:01 and T1D onset age. In conclusion, the data showed that HLA class I alleles play a role in susceptibility to T1D with different onset ages among Chinese patients, which is independent from DR-DQ haplotypes. Disclosure Z. Jiang: None. W. Ren: None. Y. Xian: None. J. Yan: None. D. Yang: None. S. Luo: None. X. Zheng: None. W. Xu: None. J. Bei: None. L. Groop: None. J. Weng: None. Funding National Natural Science Foundation of China (81530025); National Key Research and Development Program of China (2017YFC1309603); Sun Yat-sen University (2007030)

Background: The relation of CGM derived parameters and adverse pregnancy outcomes (APOs) in pregnant women with type 1 diabetes (T1D) is not completely clear. Methods: During 2015 - 2018, data were prospectively collected from pregnancies of women with pregestational T1D receiving intermittent CGM in 11 centers in China. Characteristics and CGM derived parameters were compared between the women who had severe APOs and those who did not. Severe APOs were defined as maternal death, neonatal death, congenital anomaly, pregnancy loss in 2nd/3rd trimester and neonatal admission to intensive care unit. Results: Data of 84 pregnant women with pregestational T1D were collected. Among them, 56 had received CGM in the 1st trimester, 55 in the 2nd trimester, and 59 in the 3rd trimester. 30 of these 84 women had severe APOs. Compared with women without severe APOs, women who had severe APOs had lower age at diagnosis, longer diabetes duration at conception. For CGM derived parameters, women who had severe APOs had significantly higher mean glucose (MG), MG at wake, MG at night, and time above range (TAR, >7.8mmol/L) throughout all 3 trimesters, compared with women who did not have. Details see Table. Conclusions: Higher MG, MG at wake, MG at night, and TAR throughout pregnancy were associated with the presence of severe APOs in women with T1D. These parameters should be closely monitored. Disclosure S. Luo: None. P. Ling: None. Y. Ding: None. X. Zheng: None. D. Yang: None. Y. Zhou: None. J. Yan: None. J. Weng: None. Funding National Health and Family Planning Commission of the People’s Republic of China; Foundation for Public Welfare Industry Research Project (201502011)

Background: Risk of adverse pregnancy outcomes (APOs) remains high among pregnant women with type 1 diabetes (T1D). We aimed to investigate whether implementation of a comprehensive evidence-based peri-pregnancy management plan was associated with lower rates of APOs among these women. Methods: This is a nationwide observational cohort study. A comprehensive evidence-based peri-pregnancy management plan for T1D was launched in 11 centers from 8 cities in China. During 2015-2017 we prospectively collected data from all pregnant women with T1D attending these centers. We compared pregnancy outcomes in this prospective cohort (PC) with two comparison populations. These populations were constructed by compiling data from medical records: the first was a retrospective cohort (RC) of pregnant women with T1D attending the same centers during 2012-2014 before the management plan, and the second was a comparison cohort (CC) of pregnant women with T1D receiving routine care during 2015-2017 in the comparison centers. The comparison centers were another 11 centers from 7 cities with matched socio-economic variables and medical facilities. The main outcome was severe APO comprising maternal mortality, neonatal death, congenital malformation(s), miscarriage in the 2nd trimester, and stillbirth. Results: We included a PC of 133 pregnant women with TID who received the comprehensive management during 2015-2017; a RC of 153 TID pregnancies out of 137544 pregnancies during 2012-2014; and a CC of 116 TID pregnancies out of 165493 pregnancies during 2015-2017. The rate of severe APO was significantly lower in the PC (6.02%) than either the RC (18.30%, adjusted odds ratio[aOR] 0.31, 95% CI 0.13-0.74, P Conclusions: Implementation of the comprehensive evidence-based peri-pregnancy management plan is associated with lower risk of APOs among Chinese pregnant women with T1D. Disclosure X. Zheng: None. D. Yang: None. S. Luo: None. J. Yan: None. J. Weng: None. Funding National Health and Family Planning Commission of the People’s Republic of China; Foundation for Public Welfare Industry Research Project (201502011); World Diabetes Foundation (WDF14-921)

Fulminant type l diabetes mellitus (FT1DM) is a subtype of T1DM with acute onset, but data on its feature of glucose profiles is limited. This study aimed to compare the glucose profiles between newly diagnosed patients with FT1DM and typical type 1 diabetes mellitus (TT1DM). From Sep. 2013 to Oct. 2019, newly diagnosed patients who fulfilled respective criteria of FT1DM and TT1DM in our department were included in the analysis. After diabetic ketoacidosis correction, the MiniMed Paradigm 722 insulin pump was used to monitor the real-time glucose levels for 3 consecutive days. Demographic and clinical data at the onset were collected. CGM metrics were compared between the two groups. A total of 8 patients (female, 50%) were diagnosed as FT1DM with 2 of them developed diabetes during pregnancy, and 20 patients (female, 60%) were diagnosed as TT1DM. At the onset, patients in FT1DM group had higher age (30.5 [24.0, 38.0] vs. 21.0 [9.5, 32.3] yrs, P10.0mmol/L (27.2 [16.4, 35.1] vs. 18.7 [8.7, 28.9]%) (all P>0.05).Newly diagnosed patients with FT1DM had significantly larger glycemic fluctuation than those with TT1DM even with a well-controlled inpatient management. Disclosure L. Gan: None. B. Lin: None. Y. Zhou: None. J. Yan: None. W. Xu: None. D. Yang: None. S. Luo: None. X. Zheng: None. H. Liang: None. B. Yao: None. J. Weng: None. Funding National Key Research and Development Program of China (2017YFC1309600); Natural Science Foundation of Guangdong Province (2018A030313251)

Objective: To assess the effect of use frequency of SMBG real-time decision support in a diabetes app on glycemic control in adult with T1D. Methods: T1D users from TangTangQuan® App meeting the following criteria will be selected: physician diagnosed T1D with aged≥18 years old, T1D duration ≥1 year. Frequency of uploading SMBG was be calculated in 2018. Patients were divided into two groups according to frequency of uploading SMBG (high engagement group (HE, ≥15 days/month; and control group Results: Of 3474 users over 1 year, 562 eligible patients had complete set of HbA1c records. At baseline, the mean age was 26.6±7.3 years, 33.5% were male, the mean HbA1c was 6.5±0.9%. Change in HbA1c from baseline improved in the HE group than that in control [-0.3 (-0.6, 0.2) vs. -0.1 (-0.8, 0.5) %, p=0.023]. Furthermore, Incidence of hyperglycemia at 12 months was significantly decrease in HE group than control, while no difference in Hypoglycemia between two groups (Table 1). Engagement intensity was significantly and independently associated with changes in HbA1c after adjustment by multiple regression analysis [-0.4 (-0.7, -0.0), p=0.036]. Conclusions: High engagement in SMBG real-time decision support may benefit for glycemic control in Chinese T1D adult. Disclosure Z. Liu: None. C. Wang: None. X. Zheng: None. S. Luo: None. D. Yang: None. J. Yan: None. J. Weng: None. Funding National Key Research and Development Program of China (2018YFC1314100)

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.

Background: The coronavirus disease 2019 (COVID-19) pandemic has posed a major challenge for protecting health care workers (HCWs) against the infection. Use of personal protective equipment (PPE) in health care workplace is recommended as a high priority. We aimed to investigate the relationship between PPE use and the number of COVID-19 cases among HCWs. Methods: We conducted a molecular epidemiological study through nucleic acid testing and SARS-CoV-2 specific antibody (IgM, IgG, IgA) among 142 HCWs who were dispatched from Hefei to work in Wuhan and 284 HCWs who remained in Hefei, China; both provided care for patients with COVID-19. We also extracted publicly released data on daily number of COVID-19 cases among HCWs, daily number of HCWs who were dispatched to Hubei province since January 24, and daily production of PPE in China and daily demand and supply of PPE in Hubei province. Findings: Our laboratory testing confirmed that none of the 142 HCWs who were dispatched to work in Wuhan and 284 HCWs who remained in Hefei were infected by SARS-CoV-2. Consistent with these findings, as of April 16, 2020, none of the 42,600 HCWs who were successively dispatched to Hubei province since January 24, 2020 was reported to have COVID-19. In contrast, during the early phase of COVID-19 epidemic in Hubei province, a substantial shortage of PPE and an increasing number of COVID-19 infection among HCWs were reported. With the continuing increase in domestic production of PPE in China, the PPE supply started to meet and then exceed the demand. This coincided with a subsequent reduction in the number of reported COVID-19 cases among HCWs. Interpretation: Our laboratory-confirmed findings of zero infection indicate that COVID-19 infection among HCWs could be completely prevented. Appropriate and adequate PPE might play a crucial role in protecting HCWs against COVID-19 infection. Funding Statement: This study was supported by the Fundamental Research Funds for the Central Universities (YD9110004001 and YD9110002002). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The study protocol was approved by the Institutional Review Board at the University of Science and Technology of China (USTC).

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. (Less)

Background. Fulminant type l diabetes mellitus (FT1DM) is a subtype of type 1 diabetes mellitus (T1DM) with abrupt onset, but data on its progression was limited. This study was aimed at exploring the clinical features through one-year follow-up. Methods and Materials. Patients with T1DM finishing at least one-year follow-up from June 2011 to July 2018 were enrolled from Guangdong Type 1 Diabetes Translational Medicine Study. Patients who fulfilled the respective criteria were categorized as an FT1DM group and a typical T1DM group (TT1DM). The 1 : 4 propensity score matching based on onset age, duration, and gender was performed between the FT1DM and TT1DM groups. Characteristics at the onset and after one-year follow-up were compared between the two groups. Results. A total of 53 patients with FT1DM and 212 matched patients with TT1DM were included. At the onset, there was a shorter duration of symptomatic period before diagnosis observed in the FT1DM group than in the TT1DM group (2 [1, 7] vs. 30 [10, 60] days, P<0.001). FT1DM patients had higher plasma glucose levels and higher percentage of diabetes ketoacidosis (P<0.001, respectively). Both fasting and postprandial C-peptide levels (FCP and PCP, respectively) in FT1DM were significantly lower (P<0.001). At enrollment, the duration of diabetes was 0.03 (0.00, 0.81) and 0.07 (0.00, 1.11) years and the level of HbA1c was 7.21±1.56% and 10.06±3.23% (P<0.001) in the FT1DM and TT1DM groups, respectively. After one year, both FCP and PCP were still significantly lower in the FT1DM group (P<0.001, 0.022) and the HbA1c level was similar between the two groups (P=0.128). The level of HDL-C in FT1DM was significantly higher than that in the TT1DM group at enrollment (P=0.019), and the change from enrollment was significantly greater than that in the FT1DM group (P=0.042). Conclusion. Patients with FT1DM had more severe metabolic derangement and deficiency of insulin secretion than patients with TT1DM at the onset, but glycaemic and metabolic control was not worse than that in TT1DM.

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 2 , 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 ( P = 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.

Spatial–temporal data arise frequently in biomedical, environmental, political and social science studies. Capturing dynamic changes of time-varying correlation structure is scientifically important in spatio-temporal data analysis. We approximate the time-varying empirical estimator of the spatial correlation matrix by groups of selected basis matrices representing substructures of the correlation matrix. After projecting the correlation structure matrix onto a space spanned by basis matrices, we also incorporate varying-coefficient model selection and estimation for signals associated with relevant basis matrices. The unique feature of the proposed method is that signals at local regions corresponding with time can be identified through the proposed penalized objective function. Theoretically, we show model selection consistency and the oracle property in detecting local signals for the varying-coefficient estimators. The proposed method is illustrated through simulation studies and brain fMRI data.

Background According to the current official guidelines, at least 12 lymph nodes (LNs) are qualified as an adequate sampling for colon cancer patients. However, patients evaluated with less nodes were still common in the United States, and the prevalence of positive nodal disease may be under-estimated because of the false-negative assessment. In this study, we present a statistical model that allows preoperative determination of the minimum number of lymph nodes needed to confirm a node-negative disease with certain confidence. Methods Adenocarcinoma colon cancer patients with stage T1-T3, diagnosed between 2004 and 2013, who did not receive neoadjuvant therapies and had at least one lymph node pathologically examined, were extracted from the Surveillance, Epidemiology and End Results (SEER) database. A beta binomial distribution was used to estimate the probability of an occult nodal disease is truly node-negative as a function of total number of LNs examined and T stage. Results A total of 125,306 patients met study criteria; and 47,788 of those were node-positive. The probability of falsely identifying a patient as node-negative decreased with an increasing number of nodes examined for each stage, and was estimated to be 72% for T1 and T2 patients with a single node examined and 57% for T3 patients with a single node examined. To confirm an occult nodal disease with 90% confidence, 3, 8, and 24 nodes need to be examined for patients from stage T1, T2, and T3, respectively. Conclusions The false-negative rate of diagnosed node negative, together with the minimum number of examined nodes for adequate staging, depend preoperatively on the clinical T stage. Predictive tools can recommend a threshold on the minimum number of examined nodes regarding to the favored level of confidence for each T stage. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3491-2) contains supplementary material, which is available to authorized users.

Previous data showed that poor metabolic control existed in Guangdong type 1 diabetes mellitus(T1DM) patients. Thus, scheduled follow-ups were initiated in our diabetic clinic. This study aimed to assess the effect of scheduled management and explore related factors. From June 2011 to November 2018, 342 patients with T1DM registered in our diabetic clinic. Clinical data was obtained, HbA1c and plasma lipids were measured at enrollment and then once a year. Patients who had been followed-up for three years were included. A total of 201 patients (59.7% female) were analyzed, with median age of 26.9(18.1,35.5) years and diabetic duration of 5.6(0.4,8.8) years. HbA1c levels fell from 8.0±2.0% at enrollment to 7.3±1.2% in the third year progressively (P Disclosure Y. Zhou: None. J. Yan: None. D. Yang: None. S. Luo: None. X. Zheng: None. P. Ling: None. Z. Wu: None. Q. Huang: None. Y. Xian: None. C. Wang: None. Q. Lin: None. H. Liu: None. B. Yao: None. J. Weng: None. Funding Natural Science Foundation of Guangdong Province (2018A030313251); Science and Technology Planning Project of Guangzhou (201709010037)

Objective: To develop and evaluate a smartphone-based short food frequency questionnaire. Methods: We developed a digitalized short food frequency questionnaire adapted to the diet habit of the Chinese people. Seventy participants were recruited by quota sampling. Participants completed an FFQ face to face (1st FFQ) and a 3-day dietary record (DR) at the baseline for validation. A second FFQ (2nd FFQ) was completed 3 weeks later for reproducibility study, either face to face or on the phone. Results: Sixty-seven participants completed the study per protocol and rendered eligible FFQs and 3-day DR. Twenty-one people were interviewed on the phone for 2nd FFQ and correlation coefficients of energy and nutrient intakes with 1st FFQ were 0.848∼0.959(all P Conclusion: Our FFQ had satisfying reproducibility and validity in general and diabetic population and was ready to apply to remote surveys. Disclosure D. Yang: None. C. Wang: None. S. Luo: None. X. Zheng: None. Q. Lin: None. X. Wei: None. J. Yan: None. J. Weng: None.

Objective: Data are limited on insulin resistance (IR) status in patients with type 1 diabetes (T1D). This study aimed to assess the IR status and the effect of onset age on IR in patients with T1D. Methods: Through the Guangdong T1D registry study, we identified adult patients (aged≥18 years) with a diabetes duration≥1 year. Clinical data were collected. A previously established model based on euglycemic-hyperinsulinemic clamp were used to calculate the estimated glucose disposal rate (eGDR) via clinical parameters. Participants were categorized into groups based on age of onset: childhood-onset group (cT1D, age of onset Results: This analysis included 872 adults with T1D (58.3% female). The mean (SD) eGDR was 8.98 (3.34) mg/kg/min. There was a negative correlation between the level of IR status and the onset age (r=-0.093, p=0.003). The IR status assessed by eGDR decreased alongside an increase in age of onset (p=0.018). Compared with participants with older age of onset, patients in cT1D group had a higher level of A1c, lower proportion of participants with A1c less than 7%, higher daily insulin dose and higher frequency of hypoglycemic events (all p Conclusions: Age of onset was significantly and negatively correlated with IR status. Childhood-onset patients with T1D are more likely to benefit from treatment of IR condition. Disclosure D. Yang: None. C. Wang: None. X. Zheng: None. S. Luo: None. Q. Lin: None. J. Yan: None. J. Weng: None.

The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused over 9.2 million confirmed cases and 478,000 deaths (as of June 24th, 2020). The high intensive care unit (ICU) admission rate and mortality of COVID-19 is continuously posing a serious strain on the global health-care system. While most patients present with mild to moderate symptoms, some patients may develop life-threatening sepsis, respiratory failure, acute respiratory distress syndrome (ARDS) and multiple organ failure. However, current antiviral and supportive therapies are not sufficient to prevent or treat the above complications especially in severely ill COVID-19 patients [1]. Thus, it is urgent to find the underlying mechanism dominating such life-threatening complications. It is well recognized that lung damage and multi-organ failure in this subgroup of patients arise due to overwhelming systemic hyper-inflammation. Therefore, promising anti-inflammatory candidate agents targeting diverse mechanisms related to cytokine storm will be therapeutically relevant (Fig. 1 ). Open in a separate window Fig. 1 Potential therapies of COVID-19 by targeting inflammation and cytokine storm. SARS-CoV-2 enters and infects cells by binding to TMPRSS2 and ACE2, subsequently releases virus RNA, one of the PAMPs, and recruits dendritic cells, macrophages and neutrophils. The released type I interferon and pro-inflammatory cytokines and chemokines induce the innate immune response while adaptive immune response is ignited by activating T and B lymphocytes to defend against the virus. Meanwhile, intact viruses or the components can directly activate the NLRP3 inflammasome, leading to IL-1β secretion. In most infections, moderate immune response and antiviral response are capable to combat the infection. Nevertheless, in individuals with immunological dysfunction, persistent hyper-inflammation triggers a cytokine storm, leading to the lung injury and ARDS or eventually swept through the whole body, causing MODS. During the pathological progression, the inhibition of NRLP3, JAK1/2, IL-6, BRD4 and the infusion of IVIG may be beneficial in suppressing the overwhelming inflammation and arrest or reverse the COVID-19 disease. Abbreviations: ACE2, angiotensin converting enzyme 2; ARDS, acute respiratory distress syndrome; IVIG, intravenous immunoglobulin; MODS, multiple organ dysfunction syndrome; NLRP3, Nod-like receptor protein 3; PAMP, pathogen-associated molecular pattern; TMPRSS2, transmembrane serine protease 2.

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 iPro™2 system for 14 days before HbA1c was measured at baseline, 3 months and 6 months. Data derived from iPro™2 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, p Conclusions: This study validated the GMI formula using the iPro™2 sensor in adult patients with T1D. GV influenced the relationship between GMI and laboratory HbA1c.

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) versus 7.63% (SD: 1.06), p = 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) versus 26.27 points (SD: 5.82), p = 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.

Objective: To assess the effectiveness of mobile health application TangTangQuan (TTQ) in management of type 1 diabetes (T1D) in China. Methods: TTQ is designed to provide diabetes self-management education (DSME) for patients with T1D.The innovation of TTQ is to break the isolation of individual T1D patients by socializing their self-management data, and let them find the “patients like me.” TTQ included four major modules: personal diabetes diary, games for DSME, peer support communities and online education courses. Patients recorded and uploaded their diabetes diary via TTQ, and peer patients or family members were able to make comments, or share their own experiences, or interact with the up loaders under the posts. Free download and registration of TTQ was available in major APP stores for mobiles in China since September 2015. The self-report demographic and clinical data were collected through TQQ. Results: During September 2015 and December 2017, a total of 7641 patients (M/F, 3716/3925) aged 21.28±14.43 years, with duration of T1D 2.50 (1.00,6.90) years, have signed up and joined the management of TTQ, from 21 provinces in China. Fifty two percent were 18 to 45 years old and 41% were less than 18 years old. Twenty four percent of them were active in peer support communities including sharing their experiences in management of T1D. Among 2903 patients with duration of diabetes ≥1 year who have used TTQ for ≥1 year,435 have continuous record for 1 year of self-meter blood glucose (SMBG) at least 4 times per day in TTQ. Among these patients, SMBG frequency was 2.43/week(1.40,13.13) and 2.88/week(0.63,11.92) (P=0.967), HbA1c was 6.59±1.40% and 6.40±1.39%(P=0.002), the frequency of hypoglycemia was 6.75/week (4.00,11.50) and 6.25/week (2.75,9.67) (P=0.005) before and after one year use of TTQ, respectively. Conclusions: TTQ has the potential to be a novel intervention for engaging T1D patients and their families in positive communication to support DSME. Disclosure P. Ling: None. S. Luo: None. J. Yan: None. X. Zheng: None. D. Yang: None. X. Zeng: None. J. Weng: None.