HybMED: A Hybrid Neural Network Training Processor with Multi-Sparsity Exploitation for Internet of Medical Things.

Cloud-based training and edge-based inference modes for Artificial Intelligence of Medical Things (AIoMT) applications suffer from accuracy degradation due to physiological signal variations among patients. On-chip learning can overcome this issue by online adaptation of neural network parameters for user-specific tasks. However, existing on-chip learning processors have limitations in terms of versatility, resource utilization, and energy efficiency. We propose HybMED, which is a novel neural signal processor that supports on-chip hybrid neural network training using a composite direct feedback alignment-based paradigm. HybMED is suitable for general-purpose health monitoring AIoMT devices. It improves resource utilization and area efficiency by the reconfigurable homogeneous core with heterogeneous data flow and enhances energy efficiency by exploiting sparsity at different granularities. The chip was fabricated by TSMC 40nm process and tested in multiple physiological signal processing tasks, demonstrating an average improvement in accuracy of 41.16% following online few-shot learning. The chip demonstrates an area efficiency of 1.17 GOPS/mm2 and an energy efficiency of 1.58 TOPS/W. Compared to the previous state-of-the-art physiological signal processors with on-chip learning, the chip achieves a 65× improvement in area efficiency and 1.48× improvement in energy efficiency, respectively.

A 510 µW 0.738-mm 2 6.2-pJ/SOP Online Learning Multi-Topology SNN Processor With Unified Computation Engine in 40-nm CMOS.

Implementing neural networks (NN) on edge devices enables AI to be applied in many daily scenarios. The stringent area and power budget on edge devices impose challenges on conventional NNs with massive energy-consuming Multiply Accumulation (MAC) operations and offer an opportunity for Spiking Neural Networks (SNN), which can be implemented within sub-mW power budget. However, mainstream SNN topologies varies from Spiking Feedforward Neural Network (SFNN), Spiking Recurrent Neural Network (SRNN), to Spiking Convolutional Neural Network (SCNN), and it is challenging for the edge SNN processor to adapt to different topologies. Besides, online learning ability is critical for edge devices to adapt to local environments but comes with dedicated learning modules, further increasing area and power consumption burdens. To alleviate these problems, this work proposed RAINE, a reconfigurable neuromorphic engine supporting multiple SNN topologies and a dedicated trace-based rewarded spike-timing-dependent plasticity (TR-STDP) learning algorithm. Sixteen Unified-Dynamics Learning-Engines (UDLEs) are implemented in RAINE to realize a compact and reconfigurable implementation of different SNN operations. Three topology-aware data reuse strategies are proposed and analyzed to optimize the mapping of different SNNs on RAINE. A 40-nm prototype chip is fabricated, achieving energy-per-synaptic-operation (SOP) of 6.2 pJ/SOP at 0.51 V, and power consumption of 510 µW at 0.45 V. Finally, three examples with different SNN topologies, including SRNN-based ECG arrhythmia detection, SCNN-based 2D image classification, and end-to-end on-chip learning for MNIST digit recognition, are demonstrated on RAINE with ultra-low energy consumption of 97.7nJ/step, 6.28 µJ/sample, and 42.98 µJ/sample respectively. These results show the feasibility of obtaining high reconfigurability and low power consumption simultaneously on a SNN processor.

NeuroCARE: A generic neuromorphic edge computing framework for healthcare applications.

Highly accurate classification methods for multi-task biomedical signal processing are reported, including neural networks. However, reported works are computationally expensive and power-hungry. Such bottlenecks make it hard to deploy existing approaches on edge platforms such as mobile and wearable devices. Gaining motivation from the good performance and high energy-efficiency of spiking neural networks (SNNs), a generic neuromorphic framework for edge healthcare and biomedical applications are proposed and evaluated on various tasks, including electroencephalography (EEG) based epileptic seizure prediction, electrocardiography (ECG) based arrhythmia detection, and electromyography (EMG) based hand gesture recognition. This approach, NeuroCARE, uses a unique sparse spike encoder to generate spike sequences from raw biomedical signals and makes classifications using the spike-based computing engine that combines the advantages of both CNN and SNN. An adaptive weight mapping method specifically co-designed with the spike encoder can efficiently convert CNN to SNN without performance deterioration. The evaluation results show that the overall performance, including the classification accuracy, sensitivity and F1 score, achieve 92.7, 96.7, and 85.7% for seizure prediction, arrhythmia detection and hand gesture recognition, respectively. In comparison with CNN topologies, the computation complexity is reduced by over 80.7% while the energy consumption and area occupation are reduced by over 80% and over 64.8%, respectively, indicating that the proposed neuromorphic computing approach is energy and area efficient and of high precision, which paves the way for deployment at edge platforms.

A five-parameter score for predicting saphenous vein graft degenerative and/or occlusive disease in recurring ischemic symptoms after one year post coronary artery bypass grafting.

BACKGROUND: The recurrence rate of ischemic symptoms after coronary artery bypass grafting (CABG) is increasing in recent years. How to prevent and treat saphenous vein graft disease (SVGD [symptomatic ⩾50% stenosis in at least one Saphenous vein graft]) has been a clinical challenge to date. Different pathogenesis may exist in SVGD of different periods. There are currently few available scores for estimating the risk of SVGD after one year post CABG. OBJECTIVE: We sought to develop and validate a simple predictive clinical risk score for SVGD with recurring ischemia after one year post CABG. METHODS AND RESULTS: This was a cross-sectional study and the results were validated using bootstrap resampling on a separate cohort. A nomogram and risk scoring system were developed based on retrospective data from a training cohort of 606 consecutive patients with recurring ischemia >1 year after CABG. Logistic regression model was used to find the predictive factors and to build a nomogram. To assess the generalization, models were validated using bootstrap resampling and an external cross-sectional study of 187 consecutive patients in four other hospitals. In multivariable analysis of the primary cohort, native lesion vessel number, SVG age, recurring ischemia type, very low-density lipoprotein level, and left ventricular end-diastolic diameter were independent predictors. A summary risk score was derived from nomogram, with a cut-off value of 15. In internal and external validation, the C-index was 0.86 and 0.82, indicating good discrimination. The calibration curve for probability of SVGD showed optimal agreement between actual observations and risk score prediction. CONCLUSION: A simple-to-use risk scoring system based on five easily variables was developed and validated to predict the risk of SVGD among patients who recurring ischemia after one year post CABG. This score may be useful for providing patients with individualized estimates of SVGD risk.

MSPAN: A Memristive Spike-Based Computing Engine With Adaptive Neuron for Edge Arrhythmia Detection.

In this work, a memristive spike-based computing in memory (CIM) system with adaptive neuron (MSPAN) is proposed to realize energy-efficient remote arrhythmia detection with high accuracy in edge devices by software and hardware co-design. A multi-layer deep integrative spiking neural network (DiSNN) is first designed with an accuracy of 93.6% in 4-class ECG classification tasks. Then a memristor-based CIM architecture and the corresponding mapping method are proposed to deploy the DiSNN. By evaluation, the overall system achieves an accuracy of over 92.25% on the MIT-BIH dataset while the area is 3.438 mm2 and the power consumption is 0.178 µJ per heartbeat at a clock frequency of 500 MHz. These results reveal that the proposed MSPAN system is promising for arrhythmia detection in edge devices.

Optimization of GRACE Risk Stratification by N-Terminal Pro-B-type Natriuretic Peptide Combined With D-Dimer in Patients With Non-ST-Elevation Myocardial Infarction.

We aimed to explore the utility of multiple biomarkers with GRACE risk stratification for non-ST-elevation myocardial infarction (NSTEMI). A total of 1,357 patients diagnosed with NSTEMI were enrolled in this study at multiple medical centers in Tianjin, China. The outcomes were 1-year all-cause death and major adverse cardiac events (MACE: all-cause death, hospital admission for unstable angina, hospital admission for heart failure, nonfatal recurrent myocardial infarction, and stroke). C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to verify that the biomarkers improve the predictive accuracy of the GRACE score. A total of 57 participants died, while 211 participants experienced 231 MACEs during follow-up (mean: 339 days). For all-cause death, the combination of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and D-dimer improved the predictive accuracy of GRACE the most, with C-index, IDI, and NRI values of 0.88, 0.085, and 1.223, respectively. For MACE, trigeminal combination of NT-proBNP, fibrinogen, and D-dimer resulted in C-index, IDI, and NRI values of 0.80, 0.079, and 0.647, respectively. As a result, NT-proBNP, D-dimer, fibrinogen, and GRACE comprise a new scoring system for assessing 1-year clinical events. Kaplan-Meier analysis revealed a significant increase in 1-year mortality (score ≥3.85 vs <3.85, p < 0.0001) and 1-year MACE (score ≥1.72 vs <1.72, p < 0.0001) between different score groups. In conclusion, the combination of NT-proBNP and D-dimer added prognostic value to GRACE for all-cause death. Combining NT-proBNP, fibrinogen, and D-dimer increased the prognostic value of GRACE for MACE. This newly developed scoring system is strongly correlated with all-cause mortality and MACE, and can be easily utilized in clinical practice.

Discovery and comparison of serum biomarkers for diabetes mellitus and metabolic syndrome based on UPLC-Q-TOF/MS.

INTRODUCTION: Diabetes mellitus (DM) and metabolic syndrome (MetS) are systemic metabolic disorders, which have risk factors for diabetic cardiovascular and cerebral microvascular disease. It is very important to screen the metabolic biomarkers between DM and MetS patients, which can make patients benefit to a greater extent and prevent the occurrence of disease in advance. OBJECTIVES: Diabetes mellitus (DM) and metabolic syndrome are a complex, chronic illness with a pronounced impact on the quality of life of many people. However, understanding the metabolic changes in patients and identifying high-risk individuals is crucial for prevention and disease management strategies. METHODS: In this study, a nontargeted metabolomics approach based on UPLC-Q-TOF/MS was used to find the differential metabolites in serum samples from patients with DM and MetS. RESULTS: Metabonomic analysis reveals metabolic differences between DM and HC with significant differences more than 60 metabolites. While, more than 65 metabolites have significant differences between MetS and HC. The independent disturbed pathway in the DM group was the FoxO signaling pathway. The independent disturbed pathways in the MetS group were the alpha-linolenic acid metabolism, glycerophospholipid metabolism and pyrimidine metabolism. The independent disturbed metabolites and the logistic regression result showed that betaine, alpha-linolenic acid, d-mannose, l-glutamine and methylmalonic acid can be used as a combinatorial biomarker to distinguish DM from healthy control. L-isoleucine, l-glutamine, PC(16:0/16:0), alpha-d-glucose, ketoisocaproic acid, d-mannose, uridine can be used as a combinatorial biomarker in MetS. CONCLUSION: Our findings, on one hand, provide critical insight into the pathological mechanism of DM and MetS. On the other hand, supply a combinatorial biomarker to aid the diagnosis of diseases in clinical usage.

Analysis of factors related to diabetic retinopathy in patients with newly diagnosed type 2 diabetes: a cross-sectional study.

AIM: To investigate the related factors of diabetic retinopathy (DR) and explore the correlation between smoking and DR in patients with newly diagnosed type 2 diabetes mellitus (T2DM). DESIGN: A single-centre cross-sectional study. SETTING: Tianjin 4th Central Hospital. PARTICIPANTS: Patients with newly diagnosed T2DM who visited the outpatient department of the hospital from December 2018 to April 2019. METHODS: A total of 947 patients were enrolled in the study. They were divided into two groups according to whether they were diagnosed with DR (diabetic retinopathy group, DR group; non-diabetic retinopathy group, NDR group). The smoking index (SI) was calculated to assess smoking status. Factors such as sex, age, hypertension, T2DM diagnosed age, family history of diabetes, drinking history, haemoglobin A1c (HbA1c), body mass index (BMI) and smoking status were compared between the two groups. Logistic regression was used to analyse the relationship between DR and the above factors. RESULTS: There was no statistically significant difference between the two groups in sex, age, hypertension, DM diagnosed age, family history of diabetes, drinking history and HbA1c. BMI was significantly higher in DR patients (27.7±4.2 vs 26.7±4.4, p=0.004). Smoking status was also different between the two groups (χ2=6.350, p=0.042). BMI was shown to be a related factor for DR in patients with newly diagnosed diabetes (OR=0.592, p=0.004). When BMI was ≥28 kg/m2, heavy smoking was significantly associated with DR (OR=2.219, p=0.049), and there was a negative correlation between DR and the age of diagnosis of diabetes ≥60 years (OR=0.289, p=0.009). CONCLUSIONS: Heavy smoking was an important related factor for DR in patients with newly diagnosed diabetes mellitus when BMI was ≥28 kg/m2. Delaying the age of diabetes might prevent the occurrence of DR. To elucidate the correlation, long-term cohort studies with large samples are needed.

Liraglutide promotes the angiogenic ability of human umbilical vein endothelial cells through the JAK2/STAT3 signaling pathway.

Liraglutide is a glucagon-like peptide-1 receptor (GLP-1R) agonist and incretin mimetic used for the treatment of Type 2 diabetes mellitus. It has also been shown to have a beneficial role in the cardiovascular system. Here, we investigated the mechanism by which liraglutide promotes angiogenesis using human umbilical vein endothelial cells (HUVECs). HUVECs were treated with various concentrations of liraglutide, and assessed by wound healing assay and tube formation assay as measures of angiogenesis. We found that liraglutide at 10 and 100 nmol/L greatly promoted the angiogenic ability of HUVECs. Next, we examined the JAK2/STAT3 signaling pathway and found that liraglutide treatment led to JAK2/STAT3 activation and significant increase in the angiogenic mediator expressions, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and endothelial nitric oxide synthase (eNOS) in HUVECs. Treatment with JAK2 inhibitor, AG490, in HUVECs successfully reduced the observed effects of liraglutide. We conclude that liraglutide promotes the angiogenic ability of HUVECs by activating the JAK2/STAT3 signaling pathway and upregulating its downstream factors, VEGF, bFGF and eNOS. Thus, liraglutide may provide ischemic relief for diabetic patients with cardiovascular diseases in addition to glycemic control.

Preventive Effects of Nicorandil Against Contrast-Induced Nephropathy in Patients With Moderate Renal Insufficiency Undergoing Percutaneous Coronary Intervention.

We investigated the preventive effect of nicorandil on contrast-induced nephropathy (CIN) in patients with moderate renal insufficiency undergoing percutaneous coronary intervention (PCI). A total of 250 patients with a creatinine clearance (crCl) ≤60 mL/min undergoing PCI were randomly assigned to either a nicorandil group (nicorandil 10 mg 3 times/d and hydration; n = 125) or a control group (hydration only; n = 125). The first end point was the incidence of CIN defined as an increase in serum creatinine (Scr) levels by ≥0.5 mg/dL or ≥25% within 72 hours after exposure to the contrast medium. The secondary end points were (1) changes in Scr, blood urea nitrogen, and crCl and (2) the incidence of major adverse events during hospitalization. The incidence of CIN was 1.6% (2/125) in the nicorandil group and 9.6% (12/125) in the control group (P = .011). There was no obvious difference in the incidence of major adverse events during hospitalization between the nicorandil and the control group (4.0% vs 4.8%, P = 1.000). Multivariate logistic regression analysis showed that nicorandil was a protective factor for CIN (odds ratios = 0.126, 95% confidence interval: -19.996 to -0.932, P = .012). Prophylactic administration of nicorandil may prevent against CIN in patients with moderate renal insufficiency undergoing PCI.

[Effect of miR-137 on the proliferation and apoptosis of endothelial cells regulated by AKT2 gene].

OBJECTIVE: To assess the effect of miR-137 on the proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) induced by high glucose and its mechanism. METHODS: HUVECs cells were divided into low-glucose group (5.5 mmol/L glucose-treated cells), high-glucose group (33.36 mmol/L glucose-treated cells), anti-NC group (cells treated with 33.36 mmol/L glucose after anti-NC transfection) and anti-miR-137 group (cells treated with 33.36 mmol/L glucose after anti-miR-137 transfection). After 48 hours, qRT-PCR was used to determine the expression of miR-137. CCK-8 assay and flow cytometry were used to detect cell proliferation and apoptosis rate, respectively. The targeting relationship between miR-137 and AKT2 was validated by dual fluorescence reporter gene detection system and AKT2 protein expression after overexpression or inhibition of miR-137. RESULTS: High glucose could significantly up-regulate the expression of miR-137 in HUVECs cells, and the expression of miR-137 in HUVECs cells transfected with miR-137 inhibitor was significantly decreased (P<0.05). High glucose can significantly inhibit HUVECs cell proliferation and induce apoptosis, while inhibition of miR-137 expression can weaken the effect of high glucose on HUVECs cell proliferation inhibition and apoptosis promotion (P<0.05). Inhibiting AKT2 expression could weaken the inhibitory effect of miR-137 inhibitor on HUVECs cell proliferation and apoptosis (P<0.05). CONCLUSION: Inhibiting the expression of miR-137 gene can attenuate the proliferation inhibition and apoptosis promotion of HUVECs induced by high glucose, and the mechanism is related to activating the expression of AKT2.

Liraglutide Increases VEGF Expression via CNPY2-PERK Pathway Induced by Hypoxia/Reoxygenation Injury.

Liraglutide (Lir) is a glucagon-like peptide-1 receptor agonist that lowers blood sugar and reduces myocardial infarct size by improving endothelial cell function. However, its mechanism has not yet been clarified. Unfolded protein response (UPR) plays an important role in the pathogenesis of myocardial ischemia-reperfusion injury. It determines the survival of cells. Endoplasmic reticulum position protein homologue 2 (CNPY2) is a novel initiator of UPR that also participates in angiogenesis. To this extent, the current study further explored whether Lir regulates angiogenesis through CNPY2. In our article, a hypoxia/reoxygenation (H/R) injury model of human umbilical vein endothelial cells (HUVECs) was established and the effect of Lir on HUVECs was first evaluated by the Cell Counting Kit-8. Endothelial tube formation was used to analyze the ability of Lir to induce angiogenesis. Subsequently, the effect of Lir on the concentrations of hypoxia-inducible factor 1α (HIF1α), vascular endothelial growth factor (VEGF), and CNPY2 was detected by enzyme-linked immunosorbent assay. To assess whether Lir regulates angiogenesis through the CNPY2-initiated UPR pathway, the expression of UPR-related pathway proteins (CNPY2, GRP78, PERK, and ATF4) and angiogenic proteins (HIF1α and VEGF) was detected by reverse transcription-polymerase chain reaction and Western blot. The results confirmed that Lir significantly increased the expression of HIF1α and VEGF as well as the expression of CNPY2-PERK pathway proteins in HUVECs after H/R injury. To further validate the experimental results, we introduced the PERK inhibitor GSK2606414. GSK2606414 was able to significantly decrease both the mRNA and protein expression of ATF4, HIF1α, and VEGF in vascular endothelial cells after H/R injury. The effect of Lir was also inhibited using GSK2606414. Therefore, our study suggested that the CNPY2-PERK pathway was involved in the mechanism of VEGF expression after H/R injury in HUVECs. Lir increased the expression of VEGF through the CNPY2-PERK pathway, which may promote endothelial cell angiogenesis and protect HUVEC from H/R damage.

Differences in Carotid Plaques Between Symptomatic Patients With and Without Diabetes Mellitus.

Objective- Diabetes mellitus is associated with high-risk atherosclerotic plaques. This study aimed to compare characteristics of carotid atherosclerotic plaques in symptomatic Chinese diabetic and nondiabetic patients using vessel wall magnetic resonance imaging. Approach and Results- Patients with cerebral ischemic symptoms in the anterior circulation and carotid atherosclerotic plaque determined by ultrasound were recruited from a cross-sectional, observational, multicenter study of CARE-II (Chinese Atherosclerosis Risk Evaluation). All patients underwent magnetic resonance imaging for carotid arteries. The morphological and compositional characteristics of carotid plaques were compared between diabetic and nondiabetic patients using linear (continuous variables) and logistic regression (binary variables). In a total of 584 recruited patients, 182 (31.2%) had diabetes mellitus. From the univariate analysis, diabetic patients had significantly greater mean wall area (33.7 versus 31.1 mm2; P=0.002), maximum wall thickness (3.2 versus 2.8 mm; P<0.001), and mean normalized wall index (43.8% versus 41.0%; P<0.001) and had significantly higher prevalence of calcification (51.6% versus 36.6%; P=0.001), lipid-rich necrotic core (77.5% versus 58.5%; P<0.001), and high-risk plaque (29.7% versus 19.9%; P=0.011) than nondiabetic patients. After adjusting for clinical characteristics, the differences in presence of calcification ( P=0.018) and lipid-rich necrotic core ( P=0.001) remained statistically significant. Conclusions- Symptomatic Chinese diabetic patients are more likely to have carotid plaques with calcification and lipid-rich necrotic core than nondiabetic patients, suggesting that diabetic patients may develop more severe atherosclerotic disease that should be accounted for in their clinical management.

Effects of dapagliflozin on serum uric acid levels in hospitalized type 2 diabetic patients with inadequate glycemic control: a randomized controlled trial.

BACKGROUND: Raised serum uric acid (SUA) level is commonly observed in patients with type 2 diabetes mellitus (T2DM) and is associated with increased morbidity and mortality. Sodium-glucose cotransporter 2 inhibitor, a novel oral diabetic drug, might exert a potential hypouricemic effect. We evaluated the effects of dapagliflozin on SUA levels in hospitalized T2DM patients with inadequate glycemic control. METHODS: In this randomized controlled trial, 59 T2DM hospitalized patients with inadequate glycemic control were assigned to the dapagliflozin 10 mg group (n=29) or the control group (n=30). The primary outcome was changes in SUA levels from the baseline to good glycemic control. Additional outcomes included correlations between baseline SUA levels, urinary parameters, and the changes in SUA levels. This trial is registered in the Chinese Clinical Trial Registry (number ChiCTR1800015830). RESULTS: Compared to baseline level, SUA levels had significantly decreased in both groups (P<0.001 for the dapagliflozin group and P=0.013 for the control group). Mean changes from baseline in SUA levels for dapagliflozin vs the control group were 68.03 vs 25.90 µmol/L (P=0.0406). Adjusted mean SUA levels were lower in the dapagliflozin group (273.28 vs 307.57 µmol/L; P=0.0089). In T2DM patients treated with dapagliflozin, the decrease in SUA levels was positively correlated with baseline SUA levels (P<0.0001) but not correlated with changes in 24-hour urine volume, 24-hour urine glucose, or 24-hour urinary uric acid. CONCLUSION: Dapagliflozin could improve glycemic control and lower SUA levels in hospitalized patients with uncontrolled T2DM. Longer-time trials are required to further demonstrate the hypouricemic effect of dapagliflozin and explore the potential underlying mechanisms.

Dexmedetomidine alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress dependent apoptosis through the PERK-CHOP-Caspase-11 pathway.

Dexmedetomidine (Dex) has the neuroprotective effect on cerebral ischemia-reperfusion injury (CIRI). But the mechanism is not yet clear. In this study, we established a model of middle cerebral artery occlusion (MCAO) and treated primary cortical neurons with oxygen glucose deprivation (OGD), followed by Dex treatment. Neurological protection of Dex was then assessed by neurological deficit score, brain edema, TTC staining, TUNEL assay, Western blot analysis, immunohistochemistry, and RT-PCR. The results showed that Dex significantly reduced the neurological deficit score, brain edema and cerebral infarction area due to CIRI. After Dex treatment, the expression levels of ER stress-related apoptosis pathway proteins (GRP78, p-PERK, CHOP and Cleaved-caspase-3) were significantly decreased and the apoptosis of brain cells was also significantly reduced. Immunohistochemistry showed that expression and nuclear localization of CHOP decreased significantly after the application of Dex. The downstream apoptotic protein caspase-11 mediated by PERK-CHOP was also markedly inhibited by Dex. In conclusion, our results suggested that Dex reduced ER stress-induced apoptosis after CIRI. Its protective mechanism may be related to PERK-CHOP-Caspase-11 dependent signaling pathway.

Effects of telmisartan on TNFα induced PPARγ phosphorylation and insulin resistance in adipocytes.

BACKGROUND: Telmisartan is an angiotensin II receptor blocker (ARB) and a partial agonist of peroxisome proliferator activated receptor γ (PPARγ). It has been shown to significantly enhance insulin sensitivity in clinical studies and in vitro experiments. However, the effect of telmisartan on PPARγ in adipocytes remains unknown. METHODS: 3T3-L1 adipocytes were incubated with tumor necrosis factor α (TNFα) to simulate growth under an inflammatory condition. On this basis, adipocytes were treated with telmisartan at different concentrations for 1 h. Then, the phosphorylation level of PPARγ, glucose uptake, mRNA levels of PPARγ downstream genes and adiponectin secretion of adipocytes were analyzed. RESULTS: Telmisartan reduced the phosphorylation level of PPARγ, altered mRNA expressions of adiponectin, adipsin, leptin, FABP4, GLUT4 and CAP, and promoted the secretion of adiponectin. Furthermore, telmisartan treatment restored the decrease of cellular glucose uptake due to TNFα stimulation. CONCLUSIONS: Telmisartan regulated PPARγ phosphorylation and its downstream gene expressions, promoted glucose uptake and acted as an overall insulin sensitizing agent in adipocytes. The specific phosphorylation site of PPARγ affected by telmisartan, the mechanism of telmisartan in regulating PPARγ phosphorylation, and whether the effects of telmisartan in adipocytes is responsible for its whole-body insulin sensitizing effect require further exploration.

Efficacy of alprostadil in preventing contrast-induced nephropathy in patients undergoing percutaneous coronary intervention: A multicenter prospective randomized controlled trial.

BACKGROUND: The role of alprostadil on the prevention of contrast-induced nephropathy (CIN) still remains controversial. The purpose of this study was to examine the effects of short-term alprostadil on the incidence of CIN in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: A total of 480 patients with coronary heart disease undergoing PCI were enrolled in our study and randomly assigned to two groups. The control group (n = 240) was given only hydration therapy and the alprostadil group (n = 240) received intravenous administration of 20 ug/day (diluted with 100 ml normal saline) from 0.5∼1 hr before to 3 days after operation on the basis of hydration. The primary endpoint of the study was the incidence of CIN, which was defined as an increase in SCr concentration ≥ 44.2 umol/l or ≥25% above baseline within 48 hr∼72 hr after exposure of contrast media. RESULTS: The incidence of CIN was significantly lower in the alprostadil group than that in the control group (6.25% vs 11.67%, P = 0.038). Multivariate logistic regression analysis showed that alprostadil was the protective factor of CIN (OR = 0.699, 95% CI 0.542-0.902, P = 0.006). The benefits against CIN were consistent in prespecified high-risk patients with diabetes mellitus (P = 0.003). In addition, we also found that hs-CRP and blood homocysteine values after PCI were significantly lower in the alprostadil group than those in the control group. CONCLUSION: Prophylactic administration of alprostadil may prevent against CIN in coronary heart disease patients undergoing elective PCI, particularly in high-risk patients with diabetes mellitus.

Preventive Effects of Alprostadil Against Contrast-Induced Nephropathy Inpatients With Renal Insufficiency Undergoing Percutaneous Coronary Intervention.

We investigated the preventive effect of alprostadil on contrast-induced nephropathy (CIN) in patients with renal insufficiency undergoing percutaneous coronary intervention (PCI). A total of 300 patients with creatinine clearance (crCl) ≤60 mL/min undergoing PCI were randomly assigned to alprostadil or a control group. The primary end point was the incidence of CIN defined as an increase in serum creatinine (Scr) levels by ≥0.5 mg/dL or≥ 25% after administration of the contrast media within 72 hours. The secondary end points were (1) changes in Scr and crCl within 72 hours and (2) the incidence of major adverse events during hospitalization. The incidence of CIN was 2.7% (4/150) in the alprostadil group, and 8.7% (13/150) in the control group (χ2 = 5.05, P = .043).There was no difference regarding the incidence of major adverse events during hospitalization between the alprostadil group and control groups (2.7% vs 4.0%, P = .750). Multivariate logistic regression analysis showed that alprostadil was an independent protective factor for CIN (odds ratio = 0.136, 95% confidence interval: 0.020-0.944, P = .044). Prophylactic administration of alprostadil may prevent CIN in patients with renal insufficiency undergoing PCI.

The efficacy of probucol combined with hydration in preventing contrast-induced nephropathy in patients with coronary heart disease undergoing percutaneous coronary intervention: a multicenter, prospective, randomized controlled study.

PURPOSE: To investigate the preventive effect of probucol combined with hydration on contrast-induced nephropathy (CIN) in patients with coronary heart disease undergoing percutaneous coronary intervention (PCI). METHODS: A total of 641 patients undergoing PCI were randomly assigned to either a probucol group (probucol 500 mg twice daily and hydration; n = 321) or a control group (hydration only; n = 320). The primary endpoint was the incidence of CIN, defined as an increase in serum creatinine (Scr) by ≥ 44.2 µmol/L or ≥ 25% within 72 h after the administration of contrast agent. Secondary endpoints were changes in Scr, cystatin-C (Cys-C), creatinine clearance rate (Ccr), C-reactive protein (CRP), superoxide dismutase (SOD), and glutathione (GSH) within 72 h, and major adverse events during hospitalization or the 14-day follow-up period. RESULTS: The incidence of CIN was 4.0% (13/321) in the probucol group and 10.9% (35/320) in the control group. The probucol group had lower Cys-C and higher Ccr at 48 and 72 h after PCI compared with the control group. At 48 and 72 h following the operation, Cys-C and CRP were lower in the probucol group compared with the control group, but Ccr, SOD, and GSH were higher. There were no differences in the incidence of major adverse events during hospitalization or the 14-day follow-up between the groups. Multivariate logistic regression analysis showed that probucol was an independent protective factor for CIN. CONCLUSIONS: Probucol combined with hydration more effectively decreased the incidence of CIN in patients with coronary heart disease undergoing PCI compared with hydration alone.