Fibrate and the risk of cardiovascular disease among moderate chronic kidney disease patients with primary hypertriglyceridemia

IntroductionHypertriglyceridemia is the most prevalent dyslipidemia in patients with chronic kidney disease (CKD). However, research about fibrate treatment in CKD patients is limited, and assessing its benefits becomes challenging due to the frequent concurrent use of statins. Thus, this study is aimed to investigate the role of fibrate in CKD stage 3 patients with hypertriglyceridemia who did not receive other lipid-lowering agents.MethodsThis study enrolled patients newly diagnosed CKD3 with LDL-C<100mg/dL and had never received statin or other lipid-lowering agents from Chang Gung Research Database. The participants were categorized into 2 groups based on the use of fibrate: fibrate group and non-fibrate group (triglyceride >200mg/dL but not receiving fibrate treatment). The inverse probability of treatment weighting was performed to balance baseline characteristics.ResultsCompared with the non-fibrate group (n=2020), the fibrate group (n=705) exhibited significantly lower risks of major adverse cardiac and cerebrovascular events (MACCEs) (10.4% vs. 12.8%, hazard ratios [HRs]: 0.69, 95% confidence interval [CI]: 0.50 to 0.95), AMI (2.3% vs. 3.9%, HR: 0.52, 95% CI: 0.37 to 0.73), and ischemic stroke (6.3% vs. 8.0%, HR: 0.67, 95% CI: 0.52 to 0.85). The risk of all-cause mortality (5.1% vs. 4.5%, HR: 1.09, 95% CI: 0.67 to 1.79) and death from CV (2.8% vs. 2.3%, HR: 1.07, 95% CI: 0.29 to 2.33) did not significantly differ between the 2 groups.ConclusionThis study suggests that, in moderate CKD patients with hypertriglyceridemia but LDL-C < 100mg/dL who did not take other lipid-lowering agents, fibrates may be beneficial in reducing cardiovascular events

Alternative Complement Pathway Is Activated and Associated with Galactose-Deficient IgA1 Antibody in IgA Nephropathy Patients

BackgroundGalactose-deficient IgA1 (Gd-IgA1) and alternative complement pathway activation are considered to be involved in the pathogenesis of IgA nephropathy (IgAN). Nevertheless, the relationships between alternative pathway activation and disease activity or Gd-IgA1 level remains unclear.MethodsNinety-eight biopsy-diagnosed IgAN, twenty-five primary focal segmental sclerosis (FSGS) patients and forty-two healthy individuals were recruited in this study. Among them, fifty IgAN patients received immunosuppression. Follow-up blood samples at 1 and 3~6 months after immunosuppression were collected. Plasma levels of complement C5a, factor Ba and Gd-IgA1 were measured and analyzed. Immunostaining for complement was performed in twenty-five IgAN and FSGS patients.ResultsAt baseline, IgAN patients had higher levels of plasma C5a, factor Ba and Gd-IgA1 than control subjects. Gd-IgA1 levels positively correlated with plasma C5a and factor Ba. In addition, levels of factor Ba and Gd-IgA1 were positively associated with proteinuria and negatively associated with renal function. Immunostaining revealed positive staining for factor Bb and C3c in glomeruli in IgAN patients, but not in FSGS patients. At baseline, patients receiving immunosuppression had more severe proteinuria and higher factor Ba. After 6 months, eGFR declined and proteinuria persisted in patients without immunosuppression. In contrast, patients who received immunosuppression exhibited decreased plasma levels of C5a, factor Ba, and Gd-IgA1 as early as 1 month after treatment. Proteinuria decreased and renal function also remained stable 6 months after immunosuppression.ConclusionsOur results indicate a close relationship between alternative complement pathway activation, Gd-IgA1 concentration and clinical severity of IgAN. Level of complement factor B may be a potential marker for disease activity and therapeutic target in IgAN patients

Induction of Bcl-2 Expression by Hepatitis B Virus Pre-S2 Mutant Large Surface Protein Resistance to 5-Fluorouracil Treatment in Huh-7 Cells

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis due to resistance to conventional chemotherapy and limited efficacy of radiotherapy. Our previous studies have indicated that expression of Hepatitis B virus pre-S2 large mutant surface antigen (HBV pre-S2Δ) is associated with a significant risk of developing HCC. However, the relationship between HBV pre-S2Δ protein and the resistance of chemotherapeutic drug treatment is still unclear. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that the expression of HBV pre-S2Δ mutant surface protein in Huh-7 cell significantly promoted cell growth and colony formation. Furthermore, HBV pre-S2Δ protein increased both mRNA (2.7±0.5-fold vs. vehicle, p=0.05) and protein (3.2±0.3-fold vs. vehicle, p=0.01) levels of Bcl-2 in Huh-7 cells. HBV pre-S2Δ protein also enhances Bcl-2 family, Bcl-xL and Mcl-1, expression in Huh-7 cells. Meanwhile, induction of NF-κB p65, ERK, and Akt phosphorylation, and GRP78 expression, an unfolded protein response chaperone, were observed in HBV pre-S2Δ and HBV pre-S-expressing cells. Induction of Bcl-2 expression by HBV pre-S2Δ protein resulted in resistance to 5-fluorouracil treatment in colony formation, caspase-3 assay, and cell apoptosis, and can enhance cell death by co-incubation with Bcl-2 inhibitor. Similarly, transgenic mice showed higher expression of Bcl-2 in liver tissue expressing HBV pre-S2Δ large surface protein in vivo. CONCLUSION/SIGNIFICANCE: Our result demonstrates that HBV pre-S2Δ increased Bcl-2 expression which plays an important role in resistance to 5-fluorouracil-caused cell death. Therefore, these data provide an important chemotherapeutic strategy in HBV pre-S2Δ-associated tumor

A Genome-Wide Association Study Identifies Susceptibility Variants for Type 2 Diabetes in Han Chinese

To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54×10−10; odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36–1.82), and serine racemase (SRR) (P = 3.06×10−9; OR = 1.28; 95% CI = 1.18–1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65×10−10; OR = 1.29, 95% CI = 1.19–1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations

A room temperature surface acoustic wave CO sensor based on Au-coated ZnO nanorods

近年來，隨著生活水準的提昇,環境空氣品質在工業以及住家環境中，對於人體健康的影響日益重要。一氧化碳是碳氫化合物燃燒不完全所產生的一種無色，無味以及無刺激性的有毒氣體，因為其不易察覺的特性使得因一氧化碳危害人體生命安全的事件層出不窮，此外，一氧化碳也會對燃料電池中作為電極的貴重金屬如白金造成毒化的現象。有鑑於此，對於一氧化碳氣體有高靈敏度，快速反應以及高穩定度的監測系統為現今一氧化碳感測科技發展的方向。去對於一氧化碳感測器的研究主要是利用半導體金屬氧化物來當作感測材料，並結合奈米結構的優點來進行量測。實驗的結果顯示這些感測器操作的溫度絕多數在80°C以上，需要加熱器，有著較大的能量消耗等缺點。由於表面聲波式之感測器對於表面的物理量變動相當靈敏，因此非常適合用來作為一氧化碳室溫下的感測平台。本論文中‭，首先製作一組中心頻率為145 MHz以128°YX-LiNbO3 當作基底的表面聲波振盪器‭，使用氧化鋅奈米柱與奈米金粒子之結合來作為一氧化碳感測的材料並以週期性之結構塗佈於表面聲波共振器表面‭。此外，使用雙振盪器之量測架構來降低環境擾動所造成的影響。由於氧化鋅奈米柱具有較大的表面積對體積比，較快的電子擴散速率以及奈米金粒子在室溫下對一氧化碳的觸媒特性，實驗結果顯示表面聲波式之一氧化碳感測器在室溫下有良好靈敏度，穩定度以及快速反應之感測性質，實為未來攜帶型一氧化碳監測系統一個很好的選擇。There is a growing demand for developing a sensing system to measure carbon monoxide (CO) not only for industry applications but also for human health in the recent years. CO is generated from the combustion of the organic matter with insufficient oxygen supply, which is colorless, odorless and tasteless. Moreover, CO is able to poison the noble metals making poor performance on the catalyst like Pt used in fuel cells. Due to the fatal danger and poisoning effect, the demand for CO detection at room temperature with high sensitivity, stability, selectivity and short response time is urgently required.he previous research of the CO sensor employed the variety of sensing material as the metal oxide semiconductor with various nanostructure, and most of them showed the operating temperature higher than 80?C causing large power consumption and problems of size reduction of the heater circuit. Since the surface acoustic wave (SAW) sensor device having high sensitivity to the surface perturbation, a CO SAW sensor based on Au-coated ZnO nanorods is realized to pursue the goals of CO detection at the room temperature. In the thesis, a SAW resonator is fabricated on 128?YX-LiNbO3 with the central frequency of 145 MHz. The ZnO nanorods and the adsorption of gold nanoparticles are adopted as the sensing material with periodic pattern structure coated on the delay line of the surface. A dual delay line configuration was also applied to eliminate the environmental fluctuations. Due to the ZnO nanorods posing high surface-to-volume ratio, fast charge diffusion rate and the room temperature catalyzing properties of the gold nanoparticles, we have successfully demonstrated the CO SAW sensor having fast response, high sensitivity, and short-term repeatability at room temperature, which is a good candidate for the portable CO monitoring application.Acknowledgements Ihinese Abstract IIbstract IIIists of Notations IVable of Contents VIIist of Figures IXist of Tables XIhapter 1 Introduction 11-1 Motivation 11-2 Category of Carbon Monoxide Sensors 21-3 Literature Review 41-4 Contents of the Chapters 5hapter 2 Theories of SAW Sensor 72-1 Coupling-of- Modes Model 72-1.1 [P] Matrix 72-1.2 Simulation of Two-Port SAW Filter 92-2 Sensing Mechanism of SAW sensor 122-2.1 Mass Loading Effect 122-2.2 Acoustoelectric Effect 142-2.3 Chemical Reaction 16hapter 3 Fabrication of SAW Sensor System 213-1 Configuration of SAW-based Oscillators 213-1.1 Fabrication of the SAW Resonator 21 3-1.2 Amplifier Design 23-2 Dual Channel Configuration 24-3 Fabrication of Sensing Material 253-3.1 Growth of ZnO nanorods 25-3.2 Adsorption of Au nanoparticles 26-4 Sensing Film with Periodic Pattern Structure 26hapter 4 Measurements of Au-caoted ZnO nanorods SAW CO Sensor 414-1 Experimental Configuration 414-1.1 Data Acquisition System 414-1.2 Gas Flow System 414-2 Thermal Effect 424-3 Measurement Results of SAW CO Sensors 434-3.1 Repeatability 434-3.2 Sensitivity 444-3.3 Limit of Detection 45hapter 5 Conclusion and Future Work 555-1 Conclusion 555-2 Future Work 56ppendix A 57ppendix B 60ppendix C 62eferences 6

The relationship between surface drug distribution of Dox-loaded microbubbles and drug release/cavitation behaviors with ultrasound

Ultrasound (US)-triggered microbubbles (MBs) drug delivery is a promising tool for noninvasive and localized therapy. Several studies have shown the potential of drug-loaded MBs to boost the delivery of therapeutic substances to target tissue effectively. Nevertheless, little is known about the surface payload distribution affecting the cavitation activity and drug release behavior of the drug-loaded MBs. In this study, we designed a common chemodrug (Doxorubicin, Dox)-loaded MB (Dox-MBs) and regulated the payload distribution as uniform or cluster onto the outer surface of MBs. The Dox distribution on the MB shells was assessed by confocal fluorescence microscopic imaging. The acoustic properties of the Dox-MBs with different Dox distributions were evaluated by their acoustic stability and cavitation activities. The payload release and the fragments from Dox-MBs in response to different US parameters were measured and visualized by column chromatography and cryo-electron microscopy, respectively. By amalgamating these methodologies, we found that stable cavitation was sufficient for triggering uniform-loaded MBs to release their payload, but stable cavitation and inertial cavitation were required for cluster-loaded MBs. The released substances included free Dox and Dox-containing micelle/liposome; their portions depended on the payload distribution, acoustic pressure, cycle number, and sonication duration. Furthermore, we also revealed that the Dox-containing micelle/liposome in cluster-loaded MBs had the potential for multiple drug releases upon US sonication. This study compared uniform-loaded MBs and cluster-loaded MBs to enhance our comprehension of drug-loaded MBs mediated drug delivery

The Impact of Surface Drug Distribution on the Acoustic Behavior of DOX-Loaded Microbubbles

Previous studies have reported substantial improvement of microbubble (MB)-mediated drug delivery with ultrasound when drugs are loaded onto the MB shell compared with a physical mixture. However, drug loading may affect shell properties that determine the acoustic responsiveness of MBs, producing unpredictable outcomes. The aim of this study is to reveal how the surface loaded drug (doxorubicin, DOX) affects the acoustic properties of MBs. A suitable formulation of MBs for DOX loading was first identified by regulating the proportion of two lipid materials (1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-distearoyl-sn-glycero-3-phospho-rac-glycerol sodium salt (DSPG)) with distinct electrostatic properties. We found that the DOX loading capacity of MBs was determined by the proportion of DSPG, since there was an electrostatic interaction with DOX. The DOX payload reduced the lipid fluidity of MBs, although this effect was dependent on the spatial uniformity of DOX on the MB shell surface. Loading DOX onto MBs enhanced acoustic stability 1.5-fold, decreased the resonance frequency from 12–14 MHz to 5–7 MHz, and reduced stable cavitation dose by 1.5-fold, but did not affect the stable cavitation threshold (300 kPa). Our study demonstrated that the DOX reduces lipid fluidity and decreases the elasticity of the MB shell, thereby influencing the acoustic properties of MBs

Postoperative Paraplegia as a Result of Undiagnosed Primitive Neuroectodermal Tumor, Not Epidural Analgesia

Postoperative paraplegia is a rare complication after epidural analgesia and often occurs with spinal hematoma or cord injury. We present the case of a 16-year-old girl who suffered from a tumor mass in the neck and abdomen who underwent gynecologic operation. Preoperatively, liver metastasis was found by computed tomography. Pathologic findings revealed that the abdominal mass was an ovarian dermoid cyst. After the operation, the patient complained of paraplegia while receiving epidural analgesia for postoperative pain control. A peripheral primitive neuroectodermal tumor in the thoracic and lumbar spines with spinal cord compression was later detected using magnetic resonance imaging. Learning from this case, we suggest that when a patient is preoperatively diagnosed with tumor metastasis, back pain and soreness, spinal cord compression from tumor metastasis should be excluded before epidural analgesia is implemented

Development of Anodic Titania Nanotubes for Application in High Sensitivity Amperometric Glucose and Uric Acid Biosensors

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