[Advances in the diagnosis and poor prognosis of diabetic hyperfiltration].

Glomerular hyperfiltration(GHF), as an early manifestation of prediabetes and diabetic kidney disease, occurs mainly by the mechanism of glomerular-tubular feedback and hemodynamic alterations, and the risk of hyperfiltration can be elevated in younger patients, shorter duration of the disease, poor glycemic control, and high-protein, low-salt diet. Currently, there is no recognized standard for the definition of GHF, GHF lacks typical clinical manifestations, imaging diagnostic criteria are unclear, and GHF-related laboratory markers need to be further studied. Hyperfiltration, if not diagnosed and intervened in time, can accelerate the damage of nephron and the rate of nephropathy progression, and increase the risk of complications and death. Sodium-glucose cotransporter 2 inhibitor(SGLT2i), glucagon-like peptide-1 receptor agonist(GLP-1RA)and so on can effectively reverse the hyperfiltration state. Clinical attention should be paid to the diagnosis of diabetic hyperfiltration and the prevention of its poor prognosis.

THE INCREASED PLASMA LEVELS OF INTERMEDIN IN PATIENTS WITH TYPE 2 DIABETES MELLITUS.

Context: Intermedin (IMD) is the member of calcitonin gene-related peptide family, and tightly associated with type 2 diabetes mellitus (T2DM). The change of plasma IMD levels in T2DM is still unknown. Objective: We aimed to investigate the plasma levels of IMD in patients with T2DM. Design: Fortyone patients with T2DM who were hospitalized in the endocrinology department of Civil Aviation General Hospital from January 2012 to June 2015 were enrolled, and 44 volunteers were selected as the control group. Subjects and Methods: Plasma level of IMD was detected by ELISA. Diagnostic value of IMD was analyzed by area under the receiver operating characteristic (ROC) curve (AUC). Results: The plasma level of IMD in T2DM group was higher than that in the healthy control group, whereas smoking or cardiovascular complications did no influence the IMD levels. IMD levels were correlated with BMI, DBP, triglyceride, uric acid, urea nitrogen, fasting and 2 hours postprandial blood glucose, and HbA1C. The greatest value of AUC for IMD was only 58.73%. Conclusions: Although plasma levels of IMD were increased in patients with T2DM, the very low diagnostic value of IMD for T2DM might not be used for the disease diagnosis.

[Expert consensus on the management of diabetic patients with cardiovascular diseases].

Diabetes is the most important comorbidity of cardiovascular disease, and cardiovascular disease is the main cause of mortality and disability of patients with type 2 diabetes. In order to standardize the diagnosis and treatment of patients with diabetes and cardiovascular disease, the National Health Commission Capacity Building and Continuing Education Center organized the experts from the field of cardiology and endocrinology systematically reviewing the research progresses and expert experiences of relevant disciplines from home and abroad, and formulated this consensus. This consensus covers the diagnosis, drug treatment, and risk factor management for patients with diabetes and cardiovascular disease (including atherosclerotic cardiovascular disease and heart failure) from the perspective of cardiovascular disease and diabetes management aiming to strengthen the comprehensive management of patients and ultimately to improve the prognosis of patients. The management of cardiovascular diseases mainly includes the management of blood pressure, blood lipids, anti-thrombosis, anti-myocardial ischemia, anti-ventricular remodeling and so on. Diabetes management mainly includes lifestyle intervention (including diet, exercise, weight loss, etc.), anti-hyperglycemia therapy (including drugs and insulin), blood glucose monitoring, and hypoglycemic prevention. In addition, specific clinical recommendations are given to patients with special health care needs such as diabetic nephropathy, elderly (>75 years), and cardiovascular critical illness.

Identification of heat shock protein gene expression in hair follicles as a novel indicator of heat stress in beef calves.

Heat shock proteins (HSPs) consist of highly preserved stress proteins that are expressed in response to stress. Two studies were carried out to investigate whether HSP genes in hair follicles from beef calves can be suggested as indicators of heat stress (HS). In study 1, hair follicles were harvested from three male Hanwoo calves (aged 172.2 ± 7.20 days) on six dates over the period of 10 April to 9 August 2017. These days provided varying temperature-humidity indices (THIs). In study 2, 16 Hanwoo male calves (aged 169.6 ± 4.60 days, with a BW of 136.9 ± 6.23 kg) were maintained (4 calves per experiment) in environmentally controlled chambers. A completely randomized design with a 2 × 4 factorial arrangement involving two periods (thermoneutral: TN; HS) and four THI treatment groups (threshold: THI = 68 to 70; mild: THI = 74 to 76; moderate THI = 81 to 83; severe: THI = 88 to 90). The calves in the different group were subjected to ambient temperature (22°C) for 7 days (TN) and subsequently to the temperature and humidity corresponding to the target THI level for 21 days (HS). Every three days (at 1400 h) during both the TN and HS periods, the heart rate (HR) and rectal temperature (RT) of each individual were measured, and hair follicles were subsequently collected from the tails of each individual. In study 1, the high variation (P < 0.0001) in THI indicated that the external environment influenced the HS to different extents. The expression levels of the HSP70 and HSP90 genes at the high-THI level were higher (P = 0.0120, P = 0.0002) than those at the low-THI level. In study 2, no differences in the THI (P = 0.2638), HR (P = 0.2181) or RT (P = 0.3846) were found among the groups during the TN period, whereas differences in these indices (P < 0.0001, P < 0.0001 and P < 0.0001, respectively) were observed during the HS period. The expression levels of the HSP70 (P = 0.0010, moderate; P = 0.0065, severe) and HSP90 (P = 0.0040, severe) genes were increased after rapid exposure to heat-stress conditions (moderate and severe levels). We conclude that HSP gene expression in hair follicles provides precise and accurate data for evaluating HS and can be considered a novel indicator of HS in Hanwoo calves maintained in both external and climatic chambers.

[A single center large cohort study on perioperative complications of carotid endarterectomy of 547 cases].

Objective: To analyze the risk factors of perioperative complications within 30 days of carotid endarterectomy(CEA) in the treatment of carotid atherosclerosis stenosis(CAS) during 2011-2017, and to discuss the techniques for reducing the perioperative complication rates. Methods: From August 2011 to August 2017, 486 patients with CAS were retrospective included, and 61 of them underwent bilateral CEA, with a total of 547 cases of CEA included. Perioperative complications were collected within 30 days after operation, and the risk factors related to perioperative complications were analyzed by statistical analysis. Results: In total 547 cases, 12 cases had a postoperative stroke, while 1 case died. A total of 7 cases underwent cranial nerve injury, and 5 cases had an incision related complications. In chi-square test analysis, data suggested that there was a significant difference in the incidence of complications in patients with heart disease, preoperative neurological score difference, contralateral carotid serious stenosis or occlusion and intraoperative shunt in CCA/ICA technique application (P<0.05). In the multivariate Logistic regression, it suggested that poor preoperative neurological score and contralateral carotid serious stenosis or occlusion were independent risk factors for perioperative stroke and death. Conclusion: Our results showed that CEA is effective to prevent stroke and treat patients with CAS. Patients with poor preoperative neurological score and contralateral carotid serious stenosis or occlusion may increase the risk of postoperative stroke rates.

[Effects and mechanism of apolipoprotein A5 on adipogenic differentiation of human adipose-derived mesenchymal stem cells].

Objective: To investigate the effect and related mechanism of apolipoprotein A5 (ApoA5) on adipogenic differentiation of human adipose-derived mesenchymal stem cells (AMSC). Methods: Subcutaneous adipose tissue was obtained from 40 patients undergoing abdominal surgery at our hospital from February to July 2015. After induction of human AMSC by collagenase digestion, the adipose tissue was induced to differentiate into mature adipocytes and treated with ApoA5 at 600 and 1 200 ng/ml, respectively (ApoA5 intervention groups). Cells treated without ApoA5 protein were used as control group. The cells were harvested on the 7th and 14th day of differentiation, and the following assays were performed: (1) the effect of ApoA5 on TG content was measured by a TG assay kit; (2) RT-qPCR assay was used to detect the effect of ApoA5 on aP2 and FAS mRNA expression; (3) the effect of ApoA5 on the expression of CIDEC mRNA and protein was detected by RT-qPCR and Western blot; (4) the effect of ApoA5 on the expression of C/EBPß mRNA and protein was detected by RT-qPCR and Western blot; (5) using lentiviral transfection technique, we overexpressed the gene of CIDEC in AMSC and cells were divided into lentiviral negative control group, lentiviral over-expressed CIDEC group and lentiviral over-expressed CIDEC+ApoA5 intervention group (the ApoA5 intervention concentration was 1 200 ng/ml). Thereby, we examined the effect of ApoA5 on the above indicators in adipogenic differentiation of AMSC in the case of CIDEC overexpression. Results: (1) Effect of ApoA5 on TG content in AMSC: on the 7th and 14th day after the intervention, the TG levels were lower in ApoA5 600 and 1 200 ng/ml group AMSC than those in the control group (all P<0.05). (2) The effect of ApoA5 on the expression of aP2 and FAS mRNA in AMSC: on the 7th day after intervention, the expression levels of aP2 and FAS mRNA were significantly lower in ApoA5 600 and 1 200 ng/ml group than those in the control group (all P<0.05). On the 14th day after intervention, the expression levels of aP2 and FAS mRNA were lower in ApoA5 600 and 1 200 ng/ml group than those in the control group (all P<0.05). (3) The effect of ApoA5 on the mRNA and protein expression of CIDEC in AMSC: on the 7th day after intervention, the mRNA and relative protein expression levels of CIDEC were significantly lower in AMSC of ApoA5 600 and 1 200 ng/ml group than those of the control group (all P<0.05). On the 14th day after intervention, the mRNA and relative protein levels of CIDEC were further reduced in ApoA5 600 and 1 200 ng/ml AMSC groups than those in the control group (all P<0.05). (4) The effect of ApoA5 on C/EBPß mRNA and protein expression in AMSC: on the 7th day after intervention, C/EBPß mRNA and relative protein expression levels were significantly lower in ApoA5 600 and 1 200 ng/ml group than those in the control group (all P<0.05). On the 14th day after intervention, the levels of C/EBPß mRNA and relative protein were lower in ApoA5 600 and 1 200 ng/ml group than those in the control group (all P<0.05). (5) The effect of ApoA5 on the content of TG in AMSC after CIDEC overexpression: on the 7th and 14th day after intervention, the TG contents in AMSC were higher in the lentivirus over-expressed CIDEC group than in the lentivirus negative control group (both P<0.05). However, TG contents in AMSC were similar between the over-expressed CIDEC group and the CIDEC+ApoA5 over-expression group (both P>0.05). (6) The effect of ApoA5 on the expression of aP2 and FAS mRNA in AMSC after CIDEC overexpression: on the 7th day after intervention, the expression levels of aP2 and FAS mRNA in AMSC were higher in the lentivirus over-expressed CIDEC group than in the lentivirus negative control group (both P<0.05). On the 14th day after intervention, the expression level of aP2 mRNA in the AMSC was higher in the lentivirus over-expressed CIDEC group than in the lentivirus negative control group (P<0.05). On the 7th and 14th day after intervention, the expression levels of aP2 and FAS mRNA in AMSC were similar between the lentivirus over-expressed CIDEC group and the lentivirus over-expressed CIDEC+ApoA5 group (all P>0.05). (7) The effect of ApoA5 on the expression of C/EBPß mRNA and protein in AMSC after CIDEC overexpression: on the 7th day after intervention, the mRNA and relative protein expressions of C/EBPß in AMSC were higher in lentivirus-overexpressed CIDEC group than in lentivirus negative control group (both P <0.05). On the 14th day after intervention, C/EBPß mRNA and protein expression levels in AMSC were higher in the lentivirus over-expressed CIDEC group than in the lentivirus negative control group (both P<0.05). On the 7th and 14th day after intervention, the expressions of C/EBPß mRNA and protein in AMSC were similar between lentivirus over-expressed CIDEC group and lentivirus over-expression CIDEC+ApoA5 intervention group (all P>0.05). Conclusions: ApoA5 can inhibit the adipogenic differentiation of AMSC,and this effect may be mediated by down-regulating the expression of CIDEC. Furthermore, our results indicate that CIDEC could be considered as a key factor in adipogenic differentiation.

[Effects of apolipoprotein A5 on adipogenic differentiation of human adipose mesenchymal stem cells].

Objective: To verify whether Apo A5 could inhibit the adipogenic differentiation of adipose mesenchymal stem cells (AMSCs). Methods: We isolated AMSCs by collagenase digestion method from the adipocyte tissue of patients underwent abdominal surgery in our hospital from February to July 2015. AMSCs were differentiated into mature adipocytes and incubated with Apo A5 (600 and 1 200 ng/ml) for 7, 14 and 21 days. Morphological changes, TG content, and gene expression levels of adipogenic differentiation markers were determined. Results: (1) The results of detecting the oil red O absorbance by spectrophotometer are as follows: At the 7th, 14th and 21st days after intervention, the absorbance of oil red O with 600 and 1 200 ng/ml Apo A5 intervention was lower than that of the control group (Day 7: 145.6±21.1, 110.5±31.5 vs. 195.4±35.7; Day 14: 289.2±24.2, 250.4±45.2 vs. 341.6±34.5; Day 21: 431.9±33.2, 374.7±26.4 vs. 488.2±22.5, all P<0.05). (2) The intracellular TG content after Apo A5 intervention were detected by TG quantitative detection kit detection. At the 7th, 14th and 21st days, intracellular TG contents in 600 and 1 200 ng/ml Apo A5 groups were lower than that in the control group (Day 7:(203.1±22.6), (174.2±25.8)nmol/mg protein in Apo A5 intervention group vs. (266.25±23.7)nmol/mg protein in control group; Day 14: (332.5±23.2), (231.1±22.2)nmol/mg protein in Apo A5 intervention group vs. (452.2±16.4)nmol/mg protein in control group; Day 21: (482.8±21.2), (294.2±29.9)nmol/mg protein vs. (597.2±22.1)nmol/mg protein in control group, P<0.05). (3) aP2 gene expression detected by real-time PCR and intracellular fatty acid synthase and lipid droplets coated protein gene expression levels determined by Western blot on day 7, 14 and 21 were significantly lower in Apo A5 groups than in control group (all P<0.05). Conclusions: Apo A5 significantly reduced intracellular TG content and modulated the gene expression levels of adipogenic differentiation marker, thus, Apo A5 treatment can inhibit the adipogenic differentiation of adipose mesenchymal stem cells.

High-density lipoprotein affects antigen presentation by interfering with lipid raft: a promising anti-atherogenic strategy.

Atherosclerosis is a chronic inflammatory disease. Immunomodulation of atherosclerosis emerges as a promising approach to prevention and treatment of this widely prevalent disease. The function of high-density lipoprotein (HDL) to promote reverse cholesterol transport may explain the ability of its protection against atherosclerosis. Findings that HDL and apolipoprotein A-I (apoA-I) inhibited the ability of antigen presenting cells (APCs) to stimulate T cells might be attributed to lipid raft, a cholesterol-rich microdomain exhibiting functional properties depending largely upon its lipid composition. Thus, modulating cholesterol in lipid raft may provide a promising anti-atherogenic strategy.

Phenotype-specific inhibition of the vascular smooth muscle cell cycle by high glucose treatment.

AIMS/HYPOTHESIS: Diabetes accelerates the development of atherosclerosis, which critically involves the proliferation of vascular smooth muscle cells (SMCs). However, how high glucose treatment regulates SMC proliferation is controversial. Considering the established SMC heterogeneity, we hypothesised that glucose treatment may have distinct effects on proliferation of the various phenotypic SMCs. MATERIALS AND METHODS: We tested this possibility using cloned spindle-shaped and epithelioid SMCs and laser scanning cytometry. RESULTS: Our results showed that glucose treatment significantly inhibited the serum-independent proliferation of epithelioid SMCs, but had no effect on the proliferation of spindle-shaped cells either with or without serum stimulation. Furthermore, glucose treatment inhibited DNA synthesis, as detected by bromodeoxyuridine (BrdU) incorporation, and increased the production of reactive oxygen species in epithelioid SMCs. The inhibition of BrdU incorporation by glucose treatment was mimicked by glucosamine and phorbol 2,13-dibutyrate, a protein kinase C (PKC) activator, and reversed by azaserine, an inhibitor of the hexosamine pathway. In addition, the inhibitory effects of glucose treatment were blocked by GF 109203X (a PKC inhibitor) and PD98058 (a MAPK/ERK kinase, MEK inhibitor), and by knockdown of MEK1 by small interfering RNA (siRNA). The addition of either GF 109203X or PD98058 also reduced the phosphorylation of MAP kinase induced by glucose treatment. CONCLUSIONS/INTERPRETATION: Glucose treatment inhibits the proliferation of epithelioid, but not spindle-shaped, vascular SMCs through the activation of PKC and the MAP kinase pathway, suggesting that the effects of hyperglycaemia on vascular disease depend on the phenotype of SMCs involved.

Effect of bisoprolol on QT dispersion in patients with congestive heart failure--the etiology-dependent response.

AIMS: To evaluate the effect of beta1-selective blocker bisoprolol on the QT and QTc dispersion in patients with chronic heart failure and to compare the responses to bisoprolol in patients with different etiologies. METHODS AND RESULTS: Eighty-one patients with heart failure secondary to ischemic heart disease (n=47) or idiopathic dilated cardiomyopathy (n=34) were stratified by etiology and then randomly assigned to the bisoprolol and control group (no tablet) on top of the conventional treatment. QT dispersion was calculated by subtracting the shortest QT from the longest QT, in absolute value (Qtmax-Qtmin). It was also corrected with Bazett's formula (QTc dispersion). After 6 weeks of treatment, QT and QTc dispersion were significantly decreased in the bisoprolol group (QT dispersion: 66.5+/-13.4 ms vs. 49.1+/-16.8 ms for ischemic heart disease (P<0.01); 67.5+/-12.4 ms vs. 59.4+/-14.4 ms for dilated cardiomyopathy (P<0.05); QTc dispersion: 78.3+/-15.2 ms vs. 53.3+/-18.1 ms for ischemic heart disease (P<0.01); 79.1+/-14.2 ms vs. 69.0+/-17.9 ms for dilated cardiomyopathy (P<0.05)), but there was no significant decrease of QT and QTc dispersion in the control group. Linear regression analysis showed that patients with ischemic heart disease tend to have lower 6-week QT dispersion than patients with dilated cardiomyopathy (coefficient beta=-0.283, P=0.009) after controlling for their baseline values in the bisoprolol group. CONCLUSION: These findings suggested that bisoprolol reduces QT and QTc dispersion in patients with chronic heart failure, but the etiology of heart failure affects the response of patients to bisoprolol.

Lipoprotein (a) and apolipoprotein E epsilon 4 as independent risk factors for ischemic stroke.

BACKGROUND: Controversies exist concerning the association between serum lipids and ischemic stroke. OBJECTIVE: To investigate the relationship between serum lipid, apolipoprotein E (apoE) genotype and risk of ischemic stroke. METHODS: We measured the concentrations of serum lipids, lipoprotein (a) [Lp(a)], and apoE genotype, as well as the distribution of other potential risk factors, in 90 pairs of age- and sex-matched ischemic stroke patients and stroke-free controls. RESULTS: The prevalence of hypertension, family history of stroke and hypertension, and smoking and drinking habits were significantly higher in cases than in controls. Total cholesterol, low-density lipoprotein cholesterol, and Lp(a) levels were higher in ischemic stroke patients than in controls (5.7 +/- 1.2 versus 5.3 +/- 1.2 mmol/l, P < 0.05; 3.7 +/- 1.0 versus 3.1 +/- 1.0 mmol/l, P < 0.01; and 197.6 +/- 30.6 versus 90.4 +/- 11.2 mg/l, P < 0.01, respectively). The cases had lower high-density lipoprotein cholesterol and apolipoprotein A-1 concentrations compared with the controls. The apoE epsilon 3/epsilon 4 genotype was more frequent in cases (21.1%) than in controls (8.9%, P < 0.05). CONCLUSION: The results of the study indicate that serum Lp(a) level and apoE epsilon 4 are the prominent lipidic predictors for ischemic stroke in addition to the general risk factors such as history of hypertension, family history of stroke and cigarette smoking.