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乙酰肝素酶 1

心脏代谢 1

糖尿病性心肌病 1

脂蛋白脂肪酶 1

血管内皮生长因子 1

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Hyperglycemic memory in diabetic cardiomyopathy

《医学前沿（英文）》 2022年 第16卷 第1期   页码 25-38 doi: 10.1007/s11684-021-0881-2

摘要： Cardiovascular diseases account for approximately 80% of deaths among individuals with diabetes mellitus, with diabetic cardiomyopathy as the major diabetic cardiovascular complication. Hyperglycemia is a symptom that abnormally activates multiple downstream pathways and contributes to cardiac hypertrophy, fibrosis, apoptosis, and other pathophysiological changes. Although glycemic control has long been at the center of diabetes therapy, multicenter randomized clinical studies have revealed that intensive glycemic control fails to reduce heart failure-associated hospitalization and mortality in patients with diabetes. This finding indicates that hyperglycemic stress persists in the cardiovascular system of patients with diabetes even if blood glucose level is tightly controlled to the normal level. This process is now referred to as hyperglycemic memory (HGM) phenomenon. We briefly reviewed herein the current advances that have been achieved in research on the underlying mechanisms of HGM in diabetic cardiomyopathy.

关键词： diabetes     diabetic cardiomyopathy     hyperglycemic memory    

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Clinical characteristics and outcomes of biopsy-proven diabetic nephropathy

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《医学前沿（英文）》 2017年 第11卷 第3期   页码 386-392 doi: 10.1007/s11684-017-0574-z

摘要：

Kidney damage is common in patients with diabetes mellitus (DM). However, whether the type of kidney damage can be reliably diagnosed using clinical data alone remains unclear. Predictive factors for diabetic nephropathy (DN) outcomes are also poorly understood. In this study, the clinical manifestations of 111 cases of biopsy-proven DN were described, and the clinical and pathological parameters of patients with different DN outcomes were compared. Results showed that long DM duration (>10 years in 32.4% of patients), severe proteinuria (62.2%), and renal dysfunction (estimated glomerular filtration rate [eGFR]<60 mL/(min·1.73 m2)) (52.3%) did not accurately indicate whether the condition of these patients progressed to DN. Hematuria (48.6%) failed to specify either DN or nondiabetic renal disease. Diabetic retinopathy (78.4%) was a crucial complication in patients with DN. Kaplan–Meier analysis revealed that the renal survival of 53 patients who were diagnosed with DN and were followed up was not significantly associated with glomerular classification (P>0.05). Cox’s regression analysis demonstrated that renal survival time was significantly influenced by sex (b= 1.394, P= 0.038), hematuria (b= 0.036, P= 0.029), and eGFR (b= −0.039, P= 0.002) but was not significantly affected by age, 24 h urinary protein excretion, or glomerular classification (P>0.05). In conclusion, the clinical characteristics of DN vary, and renal biopsy is necessary to determine renal damage patterns. Sex, hematuria, and the eGFR may affect DN outcomes, whereas the glomerular classification may not.

关键词： diabetic nephropathy     clinical characteristics     renal biopsy     outcomes    

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糖尿病发作后心脏脂蛋白脂肪酶的变化 Review

Chae Syng Lee, Yajie Zhai, Brian Rodrigues

《工程（英文）》 2023年 第20卷 第1期   页码 19-25 doi: 10.1016/j.eng.2022.06.013

摘要：

由于心脏持续地收缩和舒张，需要大量的能量，其中脂肪酸（FA）是其三磷酸腺苷（ATP）的主要来源。但是，心脏无法制造这种底物，而是从多种来源获得脂肪酸，包括通过脂蛋白脂肪酶（LPL）的作用。脂蛋白脂肪酶在心肌细胞中产生，随后分泌到质膜上的硫酸乙酰肝素蛋白聚糖（HSPG）结合位点。然后为了将脂蛋白脂肪酶转移到内皮细胞管腔，糖基磷脂酰肌醇锚定的高密度脂蛋白结合蛋白1（GPIHBP1）与间质性脂蛋白脂肪酶结合，并将其转移到血管管腔，在那里脂蛋白脂肪酶可将循环中的甘油三酯分解为脂肪酸。内源性-β-葡萄糖醛酸酶乙酰肝素酶（Hpa）的独特之处在于，它是唯一已知的哺乳动物酶，可以裂解硫酸乙酰肝素，从而促进上述脂蛋白脂肪酶从心肌细胞HSPG中释放。在糖尿病中，一直认为心脏产生能量方式的改变是导致糖尿病性心肌病（DCM）的原因。糖尿病发展到中度后，随着葡萄糖利用率的降低，由于Hpa 作用的增强，心脏血管腔内的脂蛋白脂肪酶活性得到增强。虽然这种适应可能有助于补偿心脏对葡萄糖的利用不足，但从长期来看，它是具有毒性的，因为有害的脂质代谢物积聚，以及脂肪酸氧化增强和因此造成的氧化应激，最终导致细胞死亡。这与一种心脏保护生长因子——血管内皮生长因子B（VEGFB）的丧失同时发生。本文探讨了乙酰肝素酶、脂蛋白脂肪酶和血管内皮生长因子B之间的相互联系及其在糖尿病性心肌病中的潜在影响。鉴于缺乏基于机制的DCM治疗，了解这种心肌病的病理，以及脂蛋白脂肪酶的作用，将有助于我们推进其临床治疗。

关键词： 心脏代谢     脂蛋白脂肪酶     乙酰肝素酶     血管内皮生长因子     糖尿病性心肌病    

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Machine learning modeling identifies hypertrophic cardiomyopathy subtypes with genetic signature

《医学前沿（英文）》 2023年 第17卷 第4期   页码 768-780 doi: 10.1007/s11684-023-0982-1

摘要： Previous studies have revealed that patients with hypertrophic cardiomyopathy (HCM) exhibit differences in symptom severity and prognosis, indicating potential HCM subtypes among these patients. Here, 793 patients with HCM were recruited at an average follow-up of 32.78 ± 27.58 months to identify potential HCM subtypes by performing consensus clustering on the basis of their echocardiography features. Furthermore, we proposed a systematic method for illustrating the relationship between the phenotype and genotype of each HCM subtype by using machine learning modeling and interactome network detection techniques based on whole-exome sequencing data. Another independent cohort that consisted of 414 patients with HCM was recruited to replicate the findings. Consequently, two subtypes characterized by different clinical outcomes were identified in HCM. Patients with subtype 2 presented asymmetric septal hypertrophy associated with a stable course, while those with subtype 1 displayed left ventricular systolic dysfunction and aggressive progression. Machine learning modeling based on personal whole-exome data identified 46 genes with mutation burden that could accurately predict subtype propensities. Furthermore, the patients in another cohort predicted as subtype 1 by the 46-gene model presented increased left ventricular end-diastolic diameter and reduced left ventricular ejection fraction. By employing echocardiography and genetic screening for the 46 genes, HCM can be classified into two subtypes with distinct clinical outcomes.

关键词： machine learning methods     hypertrophic cardiomyopathy     genetic risk    

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Normoalbuminuric diabetic kidney disease

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《医学前沿（英文）》 2017年 第11卷 第3期   页码 310-318 doi: 10.1007/s11684-017-0542-7

摘要：

Diabetic kidney disease (DKD) is one of the primary causes of end-stage renal disease (ESRD). Early diagnosis is very important in preventing the development of DKD. Urinary albumin excretion rate (UAER) and glomerular filtration rate (GFR) are widely accepted as criteria for the diagnosis and clinical grading of DKD, and microalbuminuria has been recommended as the first clinical sign of DKD. The natural history of DKD has been divided into three stages: normoalbuminuria, microalbuminuria, and macroalbuminuria. However, this clinical paradigm has been questioned recently, as studies have shown that a portion of diabetes mellitus (DM) patients with normoalbuminuria have progressive renal insufficiency, referred to as normoalbuminuric diabetic kidney disease (NADKD) or nonalbuminuric diabetic nephropathy. Epidemiologic research has demonstrated that normoalbuminuric diabetic kidney disease is common, and the large number of NADKD patients suggests that the traditional paradigm needs to be shifted. Currently, the pathogenesis of NADKD remains unclear, but many clinical studies have identified some clinical and pathological features of NADKD. In addition, the long-term outcomes of NADKD patients remain controversial. In this article, we reviewed the latest studies addressing the pathogenesis, pathology, treatment and prevention of NADKD.

关键词： diabetes     diabetic kidney disease     normoalbuminuria     renal impairment    

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Carbon dots-based fluorescence sensor for two-photon imaging of pH in diabetic mice

《化学科学与工程前沿（英文）》 2023年 第17卷 第3期   页码 298-306 doi: 10.1007/s11705-022-2212-9

摘要： Herein, a reversible pH fluorescent sensor was developed using caffeic acid as the precursor by one-step solvothermal synthesis method. The carbon dots-based sensor (CA-CDs) exhibited pH-dependent increase in fluorescence intensity and showed linear relationship in the range of pH 6.60 and 8.00. Notably, the fluorescence sensor has a reversible response to pH change. Finally, the CA-CDs has been successfully applied for two-photon imaging of the pH in liver and kidney of diabetic mice. Imaging results showed that the pH value in kidney of diabetic mice was lower than that of the normal mice, while the pH value in liver of diabetic mice was almost the same as that of the normal mice. The present study provides a simple analytical method for pH detection suitable for in vivo.

关键词： carbon dots     two-photon imaging     pH     diabetic mice    

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Non-genetic mechanisms of diabetic nephropathy

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《医学前沿（英文）》 2017年 第11卷 第3期   页码 319-332 doi: 10.1007/s11684-017-0569-9

摘要：

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetes mellitus patients and is characterized by thickened glomerular basement membrane, increased extracellular matrix formation, and podocyte loss. These phenomena lead to proteinuria and altered glomerular filtration rate, that is, the rate initially increases but progressively decreases. DN has become the leading cause of end-stage renal disease. Its prevalence shows a rapid growth trend and causes heavy social and economic burden in many countries. However, this disease is multifactorial, and its mechanism is poorly understood due to the complex pathogenesis of DN. In this review, we highlight the new molecular insights about the pathogenesis of DN from the aspects of immune inflammation response, epithelial–mesenchymal transition, apoptosis and mitochondrial damage, epigenetics, and podocyte–endothelial communication. This work offers groundwork for understanding the initiation and progression of DN, as well as provides ideas for developing new prevention and treatment measures.

关键词： diabetic nephropathy     immune inflammatory response     epithelial–mesenchymal transition     apoptosis     mitochondrial damage     epigenetics     podocyte–endothelial communication    

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Netrin-1 works with UNC5B to regulate angiogenesis in diabetic kidney disease

Xiaojing Jiao, Dong Zhang, Quan Hong, Lei Yan, Qiuxia Han, Fengmin Shao, Guangyan Cai, Xiangmei Chen, Hanyu Zhu

《医学前沿（英文）》 2020年 第14卷 第3期   页码 293-304 doi: 10.1007/s11684-019-0715-7

摘要： Netrin-1, an axon guidance factor, and its receptor UNC5B play important roles in axonal development and angiogenesis. This study examined netrin-1 and UNC5B expression in kidneys with diabetic kidney disease (DKD) and investigated their roles in angiogenesis. Netrin-1 and UNC5B were upregulated in streptozotocin-induced DKD Wistar rats, and their expression was compared with that in healthy controls. However, exogenous netrin-1 in UNC5B-depleted human renal glomerular endothelial cells (HRGECs) inhibited cell migration and tubulogenesis. This effect was likely associated with SRC pathway deactivation. Netrin-1 treatment also eliminated the pro-angiogenic effects of exogenous VEGF-165 on UNC5B-silenced HRGECs. These results indicate that UNC5B antagonizes netrin-1 and that UNC5B upregulation contributes partly to enhancing angiogenesis in DKD. Therefore, introducing exogenous netrin-1 and depleting endogenous UNC5B are potential strategies for reducing the incidence of early angiogenesis and mitigating kidney injury in DKD.

关键词： netrin-1     VEGF-165     UNC5B     angiogenesis     diabetic kidney disease    

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Sudden death due to arrhythmogenic right ventricular cardiomyopathy: Two case reports

CHEN Xinshan, ZHANG Yigu, RAO Guangxun, HUANG Guangzhao

《医学前沿（英文）》 2007年 第1卷 第3期   页码 338-342 doi: 10.1007/s11684-007-0065-8

摘要： Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a kind of primary myocardial disease characterized by the regional or global replacement of right ventricular myocardium by fatty and fibrolipomatous tissues. The ARVC, usually presenting with different clinical manifestations and pathological changes, were mainly seen in young men and is one of the main causes of sudden death in the young. Here two autopsied cases of Chinese men aged 30 and 23 years old who appeared healthy but died suddenly while at work are reported respectively. One of the victims had extensive and severe pathological changes in his heart involving the left ventricular wall as well as the ventricular septum and the right atrium. Not only was there a global fatty and fibrolipomatous tissue replacement of the right ventricular myocardia, but also mild sarcoplasmic coagulation in the myocardium and focal lymphocytic infiltration in the myocardial interstitium of the right ventricular wall. In addition, slight atherosclerosis of the coronary artery and intimal thickening of the sino-atrial node were observed. It is believed that there are no marked differences in the pathological changes of ARVC between Chinese patients and patients from western countries. The etiology and pathogenesis of ARVC could not be explained by a single cause or factor and they are probably related to various congenital and acquired causes or factors.

关键词： sarcoplasmic coagulation     acquired     ventricular myocardium     sino-atrial     autopsied    

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Familial amyloid cardiomyopathy masquerading as chronic Guillain-Barre syndrome: things are not always

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《医学前沿（英文）》 2017年 第11卷 第2期   页码 293-296 doi: 10.1007/s11684-017-0516-9

摘要：

Familial amyloid cardiomyopathy is a challenging condition that mimics many other diseases, particularly in patients with pronounced neurological presentations and unexplained or equivocal cardiac abnormalities. In this case, a 57-year-old man was admitted for outpatient cardiological evaluation of progressive right heart failure and limb paraesthesias. The patient presented with hypertension, chronic Guillain-Barre syndrome, and sick sinus syndrome. Transthoracic echocardiograms showed a thickened ventricular wall and enlarged atrium. Tissue Doppler showed a restrictive filling pattern. Transthyretin (TTR)-associated amyloidosis, which was revealed by abdominal fat-pad biopsy and DNA analysis, explained the concurrence of independent pathological features, including neuropathy and cardiac involvement. Genetic testing identified a G>T mutation in exon 4 of the transthyretin (TTR) gene. This mutation resulted in the alanine-to-serine substitution at amino acid position 117. Moreover, genetic testing confirmed that the patient’s asymptomatic son carried the same amyloidogenic TTR mutation. Given these findings, the diagnosis of familial amyloid cardiomyopathy, which was misdiagnosed as chronic Guillain-Barre syndrome, was proposed.

关键词： transthyretin (TTR) cardiac amyloidosis     sick sinus syndrome     chronic Guillain-Barre syndrome    

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Adiponectin: mechanisms and new therapeutic approaches for restoring diabetic heart sensitivity to ischemic

null

《医学前沿（英文）》 2013年 第7卷 第3期   页码 301-305 doi: 10.1007/s11684-013-0283-1

摘要：

Systemic inflammatory response following myocardial ischemia-reperfusion injury (IRI) to a specific organ may cause injuries. Ischemic post-conditioning (IPostC) has emerged as a promising method for myocardial protection against IRI both in experimental and in clinical settings. Enhancement of endogenous nitric oxide (NO) is one of the major mechanisms by which IPostC confers cardioprotection. However, the sensitivity of the diabetic heart to IPostC is impaired and the underlying mechanism is unknown. Adiponectin (APN) is an adipocyte-derived plasma protein with anti-diabetic and anti-inflammatory properties. Plasma levels of APN are decreased in obese subjects and in patients with type 2 diabetes. APN supplementation has been shown to increase NO production and attenuate myocardial IRI in normal (non-diabetic) animals. However, the effect of APN on myocardial injury in diabetic subjects, especially its potential in restoring the sensitivity of the diabetic heart to IPostC has not been investigated. In the current paper, we discussed the possible reasons why the myocardium of diabetic subjects loses sensitivity to IPostC and also highlighted the potential effectiveness and mechanism of APN in restoring IPostC cardioprotection in diabetes. This review proposes to conduct studies that may facilitate the development of novel and optimal therapies to enhance cardioprotection in patients with severe diseases such as diabetes.

关键词： adiponectin     ischemic post-conditioning     ischemia reperfusion injury     diabetes    

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Zinc homeostasis in the metabolic syndrome and diabetes

null

《医学前沿（英文）》 2013年 第7卷 第1期   页码 31-52 doi: 10.1007/s11684-013-0251-9

摘要：

Zinc (Zn) is an essential mineral that is required for various cellular functions. Zn dyshomeostasis always is related to certain disorders such as metabolic syndrome, diabetes and diabetic complications. The associations of Zn with metabolic syndrome, diabetes and diabetic complications, thus, stem from the multiple roles of Zn: (1) a constructive component of many important enzymes or proteins, (2) a requirement for insulin storage and secretion, (3) a direct or indirect antioxidant action, and (4) an insulin-like action. However, whether there is a clear cause-and-effect relationship of Zn with metabolic syndrome, diabetes, or diabetic complications remains unclear. In fact, it is known that Zn deficiency is a common phenomenon in diabetic patients. Chronic low intake of Zn was associated with the increased risk of diabetes and diabetes also impairs Zn metabolism. Theoretically Zn supplementation should prevent the metabolic syndrome, diabetes, and diabetic complications; however, limited available data are not always supportive of the above notion. Therefore, this review has tried to summarize these pieces of available information, possible mechanisms by which Zn prevents the metabolic syndrome, diabetes, and diabetic complications. In the final part, what are the current issues for Zn supplementation were also discussed.

关键词： zinc     zinc transporters     metallothionein     diabetes     diabetic complications     insulin resistance     antioxidant    

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Type 2 diabetic patients with non-alcoholic fatty liver disease exhibit significant haemorheological

Hui Dong, Fu’er Lu, Nan Wang, Xin Zou, Jingjing Rao

《医学前沿（英文）》 2011年 第5卷 第3期   页码 288-293 doi: 10.1007/s11684-011-0127-9

摘要： Haemorheological abnormalities have been described in diabetes mellitus, as well as in non-alcoholic fatty liver disease (NAFLD). However, the relationship between the changes in liver fat content and haemorheology is unknown. The current study aims to show the correlation between haemorheological parameters and intrahepatic lipid content (IHLC) in patients with type 2 diabetes. The serum biochemical markers, such as fasting plasma glucose (FPG), haemoglobin A1c (HbA1c), liver enzymes, lipid profiles, and haemorheological properties, were examined. IHLC was quantified using proton magnetic resonance spectroscopy ( H-MRS) scanning of the liver. A significant correlation was observed between IHLC and whole blood viscosity at high, middle, and low shear rates. IHLC also positively correlated with haematocrit, the reduced whole blood viscosity at low and middle shear rates, and the erythrocyte aggregation index. Diabetic patients with NAFLD exhibited significant haemorheological abnormalities compared with patients without NAFLD. In summary, haemorheological disorders are linked to non-alcoholic fatty liver in type 2 diabetes.

关键词： diabetes mellitus     type 2     haemorheology     non-alcoholic fatty liver disease    

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value of fasting glucose on the risk of heart failure and left ventricular systolic dysfunction in non-diabetic

Hui Wang, Yang Zhang, Zhujun Shen, Ligang Fang, Zhenyu Liu, Shuyang Zhang

《医学前沿（英文）》 2021年 第15卷 第1期   页码 70-78 doi: 10.1007/s11684-020-0749-x

摘要： Recent studies have shown that acute blood glucose elevation in patients with ST-segment elevation myocardial infarction (STEMI) suggests a poor prognosis. To investigate the effect of fasting blood glucose (FBG) on the risk of heart failure (HF) and left ventricular systolic dysfunction (LVSD) in non-diabetic patients undergoing primary percutaneous coronary intervention (PCI) for acute STEMI, we retrospectively recruited consecutive non-diabetic patients who underwent primary PCI for STEMI in our hospital from February 2003 to March 2015. The patients were divided into two groups according to the FBG level. A total of 623 patients were recruited with an age of 61.3±12.9 years, of whom 514 (82.5%) were male. The HF risk (odds ratio 3.401, 95% confidence interval (CI) 2.144–5.395, <0.001) was significantly increased in patients with elevated FBG than those with normal FBG. Elevated FBG was also independently related to LVSD (β 1.513, 95%CI 1.282–1.785, <0.001) in a multiple logistics regression analysis. In conclusion, elevated FBG was independently associated with 30-day HF and LVSD risk in non-diabetic patients undergoing primary PCI for STEMI.

关键词： myocardial infarction     percutaneous coronary intervention     diabetes mellitus     fasting glucose     heart failure    

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Gender differences in the relationship between plasma lipids and fasting plasma glucose in non-diabetic

null

《医学前沿（英文）》 2014年 第8卷 第4期   页码 477-483 doi: 10.1007/s11684-014-0346-y

摘要：

The association between dyslipidemia and elevated fasting glucose in type 2 diabetes is well known. In non-diabetes, whether this association still exists, and whether dyslipidemia is an independent risk factor for high fasting plasma glucose (FPG) levels are not clear. This cross-sectional study recruited 3460 non-diabetic Chinese subjects (1027 men, and 2433 women, aged 35–75 years old) who participated in a health survey. Men and women were classified into tertiles by levels of plasma lipids respectively. In women, the prevalence of impaired fasting glucose (IFG) was decreased with increased HDL-C. A stepwise increase in HDL-C was associated with decreasing FPG levels (lowest tertiles, FPG: 5.376±0.018; middle tertiles, 5.324±0.018; highest tertiles, 5.276±0.018 mmol/L; P=0.001). Reversely, FPG levels increased from lowest tertiles to highest tertiles of LDL-C, TC, and TG. we found that women in the first tertile with lower HDL-C level had a 1.75-fold increase in risk of IFG compared with non-diabetic women in the third tertile with higher HDL-C level (OR: 1.75; 95% CI: 1.20--2.56). In men, no significant association was found. We took age, BMI, waist/hip ratio, education, smoking, alcohol drinking, and physical exercise as adjusted variables. In Chinese non-diabetic women, dyslipidemia is independently associated with high levels of FPG; TG, HDL-C, and LDL-C are predictors of IFG independent of BMI and waist/hip ratio.

关键词： dyslipidemia     plasma lipids     plasma fasting glucose     impaired fasting glucose     non-diabetes    

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标题 作者 时间 类型 操作

Hyperglycemic memory in diabetic cardiomyopathy

期刊论文

Clinical characteristics and outcomes of biopsy-proven diabetic nephropathy

null

期刊论文

糖尿病发作后心脏脂蛋白脂肪酶的变化

Chae Syng Lee, Yajie Zhai, Brian Rodrigues

期刊论文

Machine learning modeling identifies hypertrophic cardiomyopathy subtypes with genetic signature

期刊论文

Normoalbuminuric diabetic kidney disease

null

期刊论文

Carbon dots-based fluorescence sensor for two-photon imaging of pH in diabetic mice

期刊论文

Non-genetic mechanisms of diabetic nephropathy

null

期刊论文

Netrin-1 works with UNC5B to regulate angiogenesis in diabetic kidney disease

Xiaojing Jiao, Dong Zhang, Quan Hong, Lei Yan, Qiuxia Han, Fengmin Shao, Guangyan Cai, Xiangmei Chen, Hanyu Zhu

期刊论文

Sudden death due to arrhythmogenic right ventricular cardiomyopathy: Two case reports

CHEN Xinshan, ZHANG Yigu, RAO Guangxun, HUANG Guangzhao

期刊论文

Familial amyloid cardiomyopathy masquerading as chronic Guillain-Barre syndrome: things are not always

null

期刊论文

Adiponectin: mechanisms and new therapeutic approaches for restoring diabetic heart sensitivity to ischemic

null

期刊论文

Zinc homeostasis in the metabolic syndrome and diabetes

null

期刊论文

Type 2 diabetic patients with non-alcoholic fatty liver disease exhibit significant haemorheological

Hui Dong, Fu’er Lu, Nan Wang, Xin Zou, Jingjing Rao

期刊论文

value of fasting glucose on the risk of heart failure and left ventricular systolic dysfunction in non-diabetic

Hui Wang, Yang Zhang, Zhujun Shen, Ligang Fang, Zhenyu Liu, Shuyang Zhang

期刊论文

Gender differences in the relationship between plasma lipids and fasting plasma glucose in non-diabetic

null

期刊论文