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Dome formation can occur in cultured tubular epithelial cells originating from various tissues, including the mammary gland and the kidney. The isolation and characterization of normal kidney epithelial stem cells that give rise to dome-forming tubular cells have never been reported. We attempted to isolate and characterize canine kidney epithelial stem cells using a simple cell culture method that we have previously used to isolate other adult human stem cells. Dome-forming kidney epithelial cells were derived from dissociated adult canine kidney tissues that were cultured in a modified keratinocyte serum-free medium supplemented with N-acetyl-l-cysteine, l-ascorbic acid 2-phosphate, nicotinamide, and fetal bovine serum. These cells exhibited high self-renewal capacity in long-term culture (growth for >13 months and 30 cumulative population doublings) and exhibited characteristics of stem cells, including (1) deficiency in gap junctional intercellular communication, (2) anchorage-independent growth, (3) expression of stem cell markers octamer-binding transcription factor 4 and SRY (sex determining region Y)-box 2, (4) expression of cell surface markers CD24 and CD133, and (5) multipotent differentiation into osteoblasts, adipocytes, chondrocytes, and dome-forming tubular cells. Most of these characteristics are shared by the well-known canine renal tubule-derived immortalized Madin-Darby Canine Kidney cell line. Furthermore, the putative canine kidney stem cells developed in this study formed budding tubule-like organoids on Matrigel and required high cell density (>4,000 cells/cm2) for sustained growth and confluency for dome formation. The signal transducer and activator of transcription-3 (STAT3) phosphorylation inhibitor, AG490, inhibited colony-forming efficiency and dome formation, whereas lipopolysaccharide, an activator of STAT3, increased colony-forming efficiency in a dose-dependent manner. These results are consistent with the hypothesis that high cell density induces STAT3 expression, which promotes both stem cell self-renewal and differentiation into tubular cells. Our novel cell culture method should be useful for the future development of normal human kidney stem cells for clinical applications and for studying mechanisms of nephrotoxicity.

Introduction: Onsite scoring is common in traditional OSCEs although there is the potential for an audience effect facilitating or inhibiting performance. We aim to (1) analyze the reliability between onsite scoring (OS) and remote scoring (RS); and (2) explore the factors that affect the scoring in different locations. Methods: A total of 154 students and 84 raters were enrolled in a single-site during 2013-2015. We selected six stations randomly from a 12-station national high-stakes OSCE. We applied generalisability theory for the analysis and investigated the perceptions that affected RS scoring. Results: The internal consistency reliability Cronbach's α of the checklists was 0.92. The kappa agreement was 0.623 and the G value was 0.93. The major source of variance comes from the students themselves, but some from locations and raters. The three-component analysis including Technical Feasibility, Facilitates Wellbeing, and Observational and Attention Deficits explained 73.886% of the total variance in RS scoring. Conclusions: Our study has demonstrated moderate agreement and good reliability between OS and RS ratings. We validated the factors of facility operation and quality for RS raters. Remote scoring can provide an alternative forum for the raters to overcome the barriers of distance, space, and avoid the audience effect.

The association between regional economic status and the probability of renal recovery among patients with dialysis-requiring AKI (AKI-D) is unknown. The nationwide prospective multicenter study enrolled critically ill adult patients with AKI-D in four sampled months (October 2014, along with January, April, and July 2015) in Taiwan. The regional economic status was defined by annual disposable income per capita (ADIPC) of the cities the hospitals located. Among the 1,322 enrolled patients (67.1 ± 15.5 years, 36.2% female), 833 patients (63.1%) died, and 306 (23.1%) experienced renal recovery within 90 days following discharge. We categorized all patients into high (n = 992) and low economic status groups (n = 330) by the best cut-point of ADIPC determined by the generalized additive model plot. By using the Fine and Gray competing risk regression model with mortality as a competing risk factor, we found that the independent association between regional economic status and renal recovery persisted from model 1 (no adjustment), model 2 (adjustment to basic variables), to model 3 (adjustment to basic and clinical variables; subdistribution hazard ratio, 1.422; 95% confidence interval, 1.022–1.977; p = 0.037). In conclusion, high regional economic status was an independent factor for renal recovery among critically ill patients with AKI-D.

Porphyromonas (P.) gingivalis infection leading to the periodontitis has been associated with the development of systemic diseases, including cardiovascular diseases and diabetes. However, the effect of a high concentration of glucose (HG) on the invasion efficiency of P. gingivalis and the consequent modulation of pathogenesis in vascular cells, especially in the vascular smooth muscle cells (VSMCs), remains unclear. Hence, the aim of this study was to investigate whether treating P. gingivalis with HG could change its invasion capability and result in VSMC calcification and the underlying mechanism. Human aortic SMCs (HASMCs) and P. gingivalis strain CCUG25226 were used in this study. We found that HGPg infection of HASMCs could initiate the HASMC calcification by stimulating the autocrine regulation of bone morphogenetic protein (BMP) 4 in HASMCs. The upregulation of BMP4 expression in HASMCs was mediated by toll-like receptor 4 and ERK1/2-p38 signaling after P. gingivalis infection. Moreover, the autocrine action of BMP4 in HGPg infection-initiated HASMC calcification upregulated BMP4-specific downstream smad1/5/8-runx2 signaling to increase the expressions of bone-related matrix proteins, that is, osteopontin, osteocalcin, and alkaline phosphatase. This study elucidates the detailed mechanism of HGPg infection-initiated calcification of HASMCs and indicates a possible therapeutic role of BMP4 in P. gingivalis infection-associated vascular calcification.

Hericium erinaceus is an edible mushroom; its various pharmacological effects which have been investigated. This study aimed to demonstrate whether efficacy of oral administration of H. erinaceus mycelium (HEM) and its isolated diterpenoid derivative, erinacine A, can act as an anti-neuroinflammatory agent to bring about neuroprotection using an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson’s disease, which results in motor disturbances, in addition to elucidating the mechanisms involved. Mice were treated with and without HEM or erinacine A, after MPTP injection for brain injuries by the degeneration of dopaminergic nigrostriatal neurons. The efficacy of oral administration of HEM improved MPTP-induced loss of tyrosine hydroxylase positive neurons and brain impairment in the substantia nigra pars compacta as measured by brain histological examination. Treatment with HEM reduced MPTP-induced dopaminergic cell loss, apoptotic cell death induced by oxidative stress, as well as the level of glutathione, nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE). Furthermore, HEM reversed MPTP-associated motor deficits, as revealed by the analysis of rotarod assessment. Our results demonstrated that erinacine A decreases the impairment of MPP-induced neuronal cell cytotoxicity and apoptosis, which were accompanied by ER stress-sustained activation of the IRE1α/TRAF2, JNK1/2 and p38 MAPK pathways, the expression of C/EBP homologous protein (CHOP), IKB-β and NF-κB, as well as Fas and Bax. These physiological and brain histological changes provide HEM neuron-protective insights into the progression of Parkinson’s disease, and this protective effect seems to exist both in vivo and in vitro.

Aim Acute kidney injury (AKI) carries an increasing incidence rate worldwide and increases the risk of developing end-stage renal disease (ESRD) as well as the medical expenses during the post-AKI course. The Taiwan Consortium for Acute Kidney Injury and Renal Diseases (CAKs) has thus launched a nationwide epidemiology and prognosis of dialysis-requiring acute kidney injury (NEP-AKI-D) study, which prospectively enrols critically ill patients with AKI. Through thoroughly evaluating the risk and prognostic factors of AKI, we hope to lower the incidence of AKI and ESRD from the perspective of AKI-ESRD interaction. Methods The CAKs includes 30 hospitals which distribute widely through the four geographical regions (north, middle, south, and east) of Taiwan, and have a 1:1 ratio of medical centres to regional hospitals in each region. The NEP-AKI-D study enrols intensive care unit-based AKI patients who receive dialysis in the four seasonal sampled months (October 2014, along with January, April, and July 2015) in the included hospitals. The collected data include demographic information, pertaining laboratory results, dialysis settings and patient outcomes. The data are uploaded in a centre website and will be audited by on-site principal investigators, computer logic gates, and the CAKs staffs. The outcomes of interest are in-hospital mortality, dialysis-dependency and readmission rate within 90 days after discharge. Conclusion The NEP-AKI-D study enrols a large number of representative AKI patients throughout Taiwan. The results of the current study are expected to provide more insight into the risk and prognostic factors of AKI and further attenuated further chronic kidney disease transition.

This article presents a compact power combiner/divider for solid-state amplifier applications inspired by spatial combiner. The proposed “one-stage” combining structure is realized by a single port tapered to an oversized microstrip connecting to parallel multiport microstrip sections. By adjusting the geometries of the structure, uniform amplitude/phase, and complex impedance matching at the multiport outputs can be achieved. A prototype 1-to-4 divider/combiner is designed and characterized at 5 GHz. Measured and simulated results showed similar trend and decent agreement. The measured combining efficiency of the circuit is 82.44% at 5 GHz. © 2016 Wiley Periodicals, Inc. Microwave Opt Technol Lett 58:1121–1125, 2016

A rectangular waveguide band-stop filter using electromagnetic crystals (EMXT) surface as the top and bottom walls is presented in this letter. The EMXT surface has a band gap that can prevent electromagnetic wave from propagating along the waveguide. Dispersion properties of the waveguide filter are analyzed using an approximated lumped-element circuit model. A W-band prototype based on the proposed waveguide filter is designed and characterized. The experimental results show a rejection band centered at 97 GHz and a rejection level of 16 dB.

This article presents a dual-band amplifier with flexible frequency ratios. The amplifier features novel Wilkinson power divider/combiner with dual-band property that allows large frequency ratio (2.16–4.9) between its first and second operating bands. The measured combining efficiency on a stand-alone combiner is 97% at 2.25 GHz and 75% at 5.25 GHz. A 2.25/5.5 GHz prototype amplifier is tested to verify dual-band functionality. Measured linear gains are 12.85 dB and 12.07 dB at the first and second frequency bands, respectively. © 2015 Wiley Periodicals, Inc. Microwave Opt Technol Lett 57:2242–2247, 2015

Background: Porphyromonas gingivalis is a major bacterial species implicated in the progression of periodontal disease, which is recognized as a common complication of diabetes. The interleukin (IL)-1b processed by the NOD-like receptor family, pyrin domain containing 3 protein (NLRP3) inflammasome has been identified as a target for pathogenic infection of the inflammatory response. However, the effect of P. gingivalis in a high-glucose situation in the modulation of inflammasome activation in human gingival fibroblasts (HGFs) is not well understood. Methods: P. gingivalis strain CCUG25226 was used to study the mechanisms underlying the regulation of HGF NLRP3 expression by the infection of high-glucose-treated P. gingivalis (HGPg). Results: HGF infection with HGPg increases the expression of IL-1b and NLRP3. We further demonstrated that the upregulation of sterol regulatory element-binding protein (SREBP)-1c by activation of the Akt and p70S6K pathways is critical for HGPg-induced NLRP3 expression. We showed that the inhibition of Janus kinase 2 (JAK2) blocks the Akt- and p70S6K-mediated SREBP-1c, NLRP3 and IL-1b expression. The effect of HGPg on HGF signaling and NLRP3 expression is mediated by b1 integrin. In addition, gingival tissues from diabetic patients with periodontal disease exhibited higher NLRP3 and SREBP-1c expression. Conclusions: Our findings identify the molecular pathways underlying HGPg-dependent NLRP3 inflammasome expression in HGFs, providing insight into the effect of P. gingivalis invasion in HGFs.

Background Pegylated interferon (peginterferon; interferon with an attached polyethylene glycol molecule) monotherapy is the recommended treatment for chronic hepatitis C virus (HCV) infection in hemodialysis patients. Limited data concerning peginterferon alfa-2b and ribavirin treatment in this population are available. Study Design 2 prospective observational cohort studies. Setting & Participants From 2007-2009, a total of 26 patients received peginterferon alfa-2b monotherapy. From 2009-2012, an additional 26 patients were treated with peginterferon alfa-2b and ribavirin. Predictors Peginterferon alfa-2b monotherapy, 1.0 μg/kg/wk, versus peginterferon alfa-2b, 1.0 μg/kg/wk, and ribavirin, 200 mg, 3 times per week. Treatment durations were 24 and 48 weeks for HCV genotypes non-1 and 1, respectively. Outcomes & Measurements End-of-treatment virologic response and sustained virologic response (SVR) were undetectable HCV RNA at the end of treatment and 24 weeks after treatment ended, respectively. SVR and treatment-related withdrawal rate were evaluated by intention-to-treat (ITT) and per-protocol (PP) analyses. Severe anemia was defined as nadir hemoglobin level Results Patients who received combination therapy had a higher end-of-treatment virologic response than patients who received monotherapy (85% vs 62% in ITT [ P = 0.03] and 100% vs 80% in PP [ P = 0.03]). The SVR rate was higher in the combination-treatment cohort than in the monotherapy cohort (62% vs 27% in ITT [ P = 0.01] and 73% vs 35% in PP [ P = 0.01]). Patients who received combination therapy had a significantly higher rate of severe anemia than those who received monotherapy (58% vs 27%; P = 0.03). However, treatment withdrawal rates were similar between the combination (15%) and monotherapy (23%) groups. Limitations Comparison of 2 sequential cohorts rather than a randomized control study. Conclusions Peginterferon alfa-2b and ribavirin combination therapy provided a higher SVR rate than peginterferon alfa-2b monotherapy for treatment-naive dialysis patients with chronic HCV infection through careful monitoring of hematologic parameters and ribavirin dose modification. Severe anemia was significantly higher in patients receiving combination therapy than patients treated with monotherapy.

Background Hericium erinaceus is an edible mushroom; its various pharmacological effects which have been investigated. This study aimed to demonstrate whether efficacy of oral administration of H. erinaceus mycelium (HEM) and its isolated diterpenoid derivative, erinacine A, can act as an anti-neuroinflammatory agent to bring about neuroprotection using an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson’s disease, which results in motor disturbances, in addition to elucidating the mechanisms involved. Methods Mice were treated with and without HEM or erinacine A, after MPTP injection for brain injuries by the degeneration of dopaminergic nigrostriatal neurons. The efficacy of oral administration of HEM improved MPTP-induced loss of tyrosine hydroxylase positive neurons and brain impairment in the substantia nigra pars compacta as measured by brain histological examination. Results Treatment with HEM reduced MPTP-induced dopaminergic cell loss, apoptotic cell death induced by oxidative stress, as well as the level of glutathione, nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE). Furthermore, HEM reversed MPTP-associated motor deficits, as revealed by the analysis of rotarod assessment. Our results demonstrated that erinacine A decreases the impairment of MPP-induced neuronal cell cytotoxicity and apoptosis, which were accompanied by ER stress-sustained activation of the IRE1α/TRAF2, JNK1/2 and p38 MAPK pathways, the expression of C/EBP homologous protein (CHOP), IKB-β and NF-κB, as well as Fas and Bax. Conclusion These physiological and brain histological changes provide HEM neuron-protective insights into the progression of Parkinson’s disease, and this protective effect seems to exist both in vivo and in vitro.

Background Hericium erinaceus is an edible mushroom; its various pharmacological effects which have been investigated. This study aimed to demonstrate whether efficacy of oral administration of H. erinaceus mycelium (HEM) and its isolated diterpenoid derivative, erinacine A, can act as an anti-neuroinflammatory agent to bring about neuroprotection using an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson’s disease, which results in motor disturbances, in addition to elucidating the mechanisms involved. Methods Mice were treated with and without HEM or erinacine A, after MPTP injection for brain injuries by the degeneration of dopaminergic nigrostriatal neurons. The efficacy of oral administration of HEM improved MPTP-induced loss of tyrosine hydroxylase positive neurons and brain impairment in the substantia nigra pars compacta as measured by brain histological examination. Results Treatment with HEM reduced MPTP-induced dopaminergic cell loss, apoptotic cell death induced by oxidative stress, as well as the level of glutathione, nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE). Furthermore, HEM reversed MPTP-associated motor deficits, as revealed by the analysis of rotarod assessment. Our results demonstrated that erinacine A decreases the impairment of MPP-induced neuronal cell cytotoxicity and apoptosis, which were accompanied by ER stress-sustained activation of the IRE1α/TRAF2, JNK1/2 and p38 MAPK pathways, the expression of C/EBP homologous protein (CHOP), IKB-β and NF-κB, as well as Fas and Bax. Conclusion These physiological and brain histological changes provide HEM neuron-protective insights into the progression of Parkinson’s disease, and this protective effect seems to exist both in vivo and in vitro.

Background: Protein-bound uremic toxins indoxyl sulfate (IS) and p-cresol sulfate (p-CS) have been implicated as an important factor in uremic syndrome. Recent evidence indicates that both IS and p-CS are predictors of cardiovascular as well as all-cause mortality among chronic dialysis patients. We conducted a study to analyze the relationship between IS and p-CS and vascular access (VA) outcome in chronic hemodialysis (HD) patients. Methods: A total of 91 chronic stable HD patients were divided into groups according to survival of VA and frequency of VA dysfunction. Demographic and biochemical data were reviewed and recorded. Serum levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1, and the total and free forms of IS and p-CS were determined. Results: Patients with a history of frequent VA failure and dysfunction had lower albumin and higher levels of ICAM-1, free IS, free and total p-CS. Diabetes was associated with higher IS and p-CS. Logistic regression revealed that diabetes and free p-CS were independent factors associated with poor outcome of VA. Conclusion: Endothelial dysfunction and uremic toxins were associated with survival and function of VA. Diabetes and free p-CS were significantly related to the outcome of VA among chronic HD patients.

Acute kidney injury (AKI) carries an increasing incidence rate worldwide and increases the risk of developing end-stage renal disease (ESRD) as well as the medical expenses during the post-AKI course. The Taiwan Consortium for Acute Kidney Injury and Renal Diseases (CAKs) has thus launched a nationwide epidemiology and prognosis of dialysis-requiring acute kidney injury (NEP-AKI-D) study, which prospectively enrols critically ill patients with AKI. Through thoroughly evaluating the risk and prognostic factors of AKI, we hope to lower the incidence of AKI and ESRD from the perspective of AKI-ESRD interaction.The CAKs includes 30 hospitals which distribute widely through the four geographical regions (north, middle, south, and east) of Taiwan, and have a 1:1 ratio of medical centres to regional hospitals in each region. The NEP-AKI-D study enrols intensive care unit-based AKI patients who receive dialysis in the four seasonal sampled months (October 2014, along with January, April, and July 2015) in the included hospitals. The collected data include demographic information, pertaining laboratory results, dialysis settings and patient outcomes. The data are uploaded in a centre website and will be audited by on-site principal investigators, computer logic gates, and the CAKs staffs. The outcomes of interest are in-hospital mortality, dialysis-dependency and readmission rate within 90 days after discharge.The NEP-AKI-D study enrols a large number of representative AKI patients throughout Taiwan. The results of the current study are expected to provide more insight into the risk and prognostic factors of AKI and further attenuated further chronic kidney disease transition.

The stromal cell-derived factor-1 (SDF-1)/CXC receptor 4 (CXCR4) axis has been shown to play a role in colorectal cancer progression. In addition, the protease urokinase-type plasminogen activator (uPA) is an important factor in tumor cell invasion and metastasis. However, the mechanism by which SDF-1 mediates uPA expression in human colorectal cancer cells remains unknown. We investigated the molecular mechanism governing the interaction between SDF-1 stimulation and uPA expression in three human colon cancer cell lines (DLD-1, SW48, and COLO 205). We found that SDF-1 stimulation led to an increase in the expression and secretion of uPA in these cells. Experiments involving specific inhibitors and small interfering RNA demonstrated that the activation of p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways are critical for SDF-1-induced uPA expression. Analysis of transcription factor binding using ELISA and chromatin immunoprecipitation assays revealed that SDF-1 increased Sp1- and AP-1-DNA-binding activities in DLD-1 cells. Inhibition of Sp1 and AP-1 activation blocked the SDF-1-induced expression and activity of the uPA promoter. The effect of SDF-1 on DLD-1 signaling and uPA expression was mediated by the CXCR4/β1 integrin axis. In summary, our findings elucidate the mechanisms of SDF-1/CXCR4 downstream signaling and provide insights into the function of SDF-1 in colon cancer cells. J. Cell. Physiol. 227: 1114–1122, 2012. © 2011 Wiley Periodicals, Inc.

In many countries low-molecular-weight heparins (LMWHs) are increasingly used for hemodialysis (HD). Low-range activated clotting time (ACT-LR) values and anti-Xa activity had been used to monitor the degree of anticoagulation caused by LMWH. However, the facilities are not easily available at most hospitals. Such data are limited in Taiwan.A total of 76 patients receiving maintenance HD were prospectively enrolled. The HD patients were randomized to receive either nadroparin or enoxaparin and checked the ACT-LR values and anti-Xa activity. We aimed to analyze ACT-LR values and anti-Xa activity along with the clotting of the dialyzer or bleeding events associated with two LMWHs after they were administered. We also aimed to determine the dose necessary to reach maximum safety and efficacy.We found no significant differences in LMWH dosage, ACT-LR values, and anti-Xa activity between the two groups. There were no significant differences in bleeding/adverse events and extracorporeal circuit thrombosis between the two groups. Most of the bleeding and adverse events were subcutaneous minor bleeding. No major bleeding or mortality was found. We found significant differences in mean dosage, cost, bleeding/adverse effect, and extracorporeal circuit thrombosis between excessive and reduced nadroparin dosage groups.LMWH is not still routinely used due to its high cost in Taiwan. In our clinical experience, nadroparin and enoxaparin exhibited high levels of safety and efficacy in chronic HD patients. Reduced LMWHs dosage could promote patient's safety and decreased HD cost in HD patients with excessive dosage of LMWHs.

Summary The type 1 fimbriae of uropathogenic Escherichia coli (UPEC) have been described as important for the establishment of bladder infections and urinary tract infections (UTI). Urinary prostaglandin (PG) levels and cyclooxygenase (COX)-2 expression in urine particulates may increase with infectious and inflammatory processes, including UTIs. We investigated the mechanisms underlying the modulation of COX-2 expression through the invasion of type 1 fimbriated UPEC strain J96 (J96-1) in human bladder 5637 cells. Bladder 5637 cells infected with J96-1 induced increases in the expression of COX-2 and secretion of PGE2. By using specific inhibitors and short hairpin RNA (shRNA), we have demonstrated that the activation of extracellular signal-related kinase (ERK), c-Jun-NH2-terminal kinase (JNK) and p38 MAPK pathways is critical for J96-1-induced COX-2 expression. Luciferase reporters and chromatin immunoprecipitation assays suggest that J96-1 invasion increases NF-κB- and AP-1-DNA-binding activities in 5637 cells. Inhibition of NF-κB and AP-1 activations blocked the J96-1-induced COX-2 promoter activity and expression. The effect of J96-1 on 5637 cell signalling and COX-2 expression is mediated by Toll-like receptor (TLR)-4. In summary, our findings provide the molecular pathways underlying type 1 fimbriated J96-dependent COX-2 expression in 5637 cells, providing insight into the function of UPEC invasion in bladder epithelial cells.

Early prediction of lamivudine (LAM) response by individualized monitoring of serum HBV DNA like roadmap concept, and investigation of the outcome after LAM discontinuation in renal transplant recipients (RTRs) with chronic hepatitis B (CHB).We conducted a study on 19 RTRs with HBV infection receiving LAM treatment for 2 years from 2004 to 2007. HBV DNA level was assessed at baseline, 12, 24, 52, and 104 weeks after treatment. Risk factors of tyrosine-methionine-aspartate-aspartate (YMDD) mutation on treatment and relapse rate of HBV after LAM discontinuation were analyzed.HBV DNA levels became undetectable in 32, 37, 63, and 53% of patients after 12, 24, 52, and 104 weeks of LAM treatment, respectively. Overall, three (16%) and five (33%) patients were detected with YMDD mutations at week 52 and 104, respectively. In the concept of roadmap, of the seven patients with inadequate virologic response (IAVR) at week 24, five had YMDD mutations. There was no significant association of YMDD mutations with age, gender, genotype, cirrhosis, HBeAg status, baseline HBV DNA, precore/core promoter mutations, and primary response, except IAVR at week 24 (P = 0.001). The relapse rate of HBV after LAM discontinuation was high (75%) during a median follow-up of 65 weeks.The rate of LAM resistance in RTRs is similar to immunocompetent CHB patients in a 2-year therapy. By roadmap concept, RTRs with IAVR require a change in therapy to prevent viral resistance. Relapse after LAM withdrawal is frequent. Long-term antiviral therapy is crucial for immunosuppressed patients.

E-selectin expression by endothelial cells (ECs) is crucial for leukocyte recruitment during the inflammatory response. Macrophage accumulation and serum E-selectin elevation are features of type 2 diabetes mellitus. However, the interactions between macrophages and ECs in regulating vascular endothelial function are not clearly understood. We investigated the mechanisms underlying the modulation of EC E-selectin expression by high glucose (HG)-treated macrophages. Macrophage-conditioned media (MCM) were prepared from HG-treated macrophages. EC stimulation with HG-MCM induced increases the expression and secretion of E-selectin. By using specific inhibitors and small interfering RNAs, we demonstrate that the activation of the JNK and p38 MAPK pathways are critical for HG-MCM-induced E-selectin expression. Transcription factor ELISA and chromatin immunoprecipitation assays further showed that HG-MCM increases the NF-κB- and AP-1 DNA-binding activities in ECs. The inhibition of NF-κB and AP-1 activation by specific siRNAs blocks the HG-MCM-induced E-selectin promoter activity and expression. Protein arrays and blocking assays using neutralizing antibodies demonstrated that macrophage inflammatory protein 1α and 1β in HG-MCM are major mediators for the induction of EC E-selectin expression. These data support the hypothesis that E-selectin up-regulation stimulated by macrophages may play an active role in atherogenesis in the HG condition and suggest a new mechanism by which arterial disease is accelerated in diabetes.

Aims: Vascular calcification is a common complication among dialysis patients and its pathogenesis involves a variety of factors. The roles of pro-inflammatory cytokines and residual kidney function (RKF) in peritoneal dialysis (PD) patients with vascular calcification have not been investigated. Materials and methods: 157 stable PD patients were enrolled. All patients had plain X-ray film examination including chest (posterior-anterior view, CXR) and pelvis. Vascular calcification was interpreted as calcified deposit over aortic arch and linear calcification of pelvic arteries. Relevant biochemical data, pro-inflammatory markers, and PD-related factors were measured and collected. Results: Vascular calcification prevalence in CXRs was higher than that in pelvis films (38.2% vs. 22.3%, p < 0.05). Patients with vascular calcification in CXR had higher incidence of calcification in pelvis films (p < 0.05). Only a minor portion (14.6%) had two calcification sites. Regression analysis revealed that age, PD duration, body mass index, and RKF were independent factors associated with vascular calcification in CXR. Age, diabetes, IL-10 and RKF were factors associated in pelvis films. Factors independently related to vascular calcification in both films were age, duration, diabetes, IL-10, and RKF. Conclusions: Besides traditional risk factors, IL-10 and RKF were important factors associated with vascular calcification in PD patients.

Objectives: To report the success of treatment with low- molecular-weight heparins (LMWHs) in a case of nephrotic syndrome complicated by mesenteric vein thrombosis (MVT) and portal vein thrombosis (PVT). Clinical Presentation and Intervention: A 53-year-old man with nephrotic syndrome developed persistent mild abdominal pain for 3 days. Hepatic-portal venous system thrombosis of nephrotic syndrome was suspected due to new-onset superficial vein engorgement of the abdomen without liver cirrhosis. Abdominal computed tomography revealed MVT concomitant with PVT. He was successfully treated with LMWH without thrombolytic therapy. After discharge on day 9, he received continuous anticoagulation by LWMH on an outpatient basis at the nephrology clinic. Venous thromboembolic events or proteinuria did not recur within the 6-month follow-up. Conclusion: This report showed a case of MVT concomitant with PVT, a critical complication of nephrotic syndrome that was diagnosed in time and successfully treated with LMWH. A high index of clinical suspicion and timely management are crucial to tackle thrombotic complications in nephrotic syndrome.

Ultrasonographic evaluation of the kidney size is a useful method for assessment of the progression and, in some cases, the type of nephropathy. Ultrasonography (USG) also plays an important role in the evaluation of both acute and chronic renal failure.To investigate the ultrasonographic appearance of the kidneys in patients with uremia, underlying renal diseases and clinical characteristics, including biological sex, were studied.This was a retrospective study of data from consecutive adult patients with uremia starting a dialysis program between January 2005 and December 2006 at the nephrology department of a university hospital in Taiwan. Kidney size was determined by USG; demographic and clinical data were obtained prior to initiation of dialysis.Of the patients (167 men, 151 women) included in the analysis, diabetes mellitus (DM) was the leading cause of uremia (127/318; 39.9%). The distribution of DM was similar between male and female patients. In addition to levels of blood urea nitrogen and hemoglobin, body mass index was similar between male and female patients (mean [SD], 22.9 [3.1] vs 22.1 [3.4] kg/m(2), respectively). Female patients had significantly lower serum creatinine levels (P0.05) and higher estimated glomerular filtration rates (P0.01) than did male patients when they initiated chronic dialysis therapy. Among those with DM, male patients were younger and had larger kidney size on initiation of dialysis therapy than did female patients (age, 59.9 [9.4] vs 64.6 [11.9] years; right renal length, 10.3 [1.4] vs 9.5 [1.5] cm; left renal length, 10.4 [1.5] vs 9.5 [1.4] cm; all, P0.05). These sex differences in age and kidney size at the start of dialysis were not observed in patients who did not have DM. Patients with DM had significantly larger kidney size than those without DM (P0.05).The kidney size of these uremic patients varied considerably, depending on sex and the underlying disease. Male patients with DM at the terminal stage of renal failure had larger kidney size and were younger at the start of dialysis therapy than female patients with DM. In uremic patients without DM, no such discrepancy was observed, and both male and female patients started dialysis therapy at a comparable age and kidney size.

Chronic inflammation is a well-recognized complication in dialysis patients and a potential role of the adipose tissue as an important tissue of origin contributing to inflammation has been proposed. Stable peritoneal dialysis (PD) patients were enrolled to investigate the relationship between serum levels of proinflammatory cytokines and adipokines. Our results revealed that there was a strong association between high sensitivity C-reactive protein and interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha) but not with IL-10 and IL-18. IL-6 correlated with TNF-alpha, IL-10, and IL-18. No association was found between IL-10 and IL-18. Adiponectin was positively correlated with all proinflammatory cytokines, except IL-10. No significant association was found between resistin and proinflammatory cytokines. Hepatocyte growth factor (HGF) was directly related to proinflammatory cytokines but not with adipokines. The presence of residual kidney function (RKF) affected IL-6, TNF-alpha, and HGF levels. The peritoneal transport property did not influence inflammatory cytokine and adipokine levels. In conclusion, there was a close relationship between proinflammatory cytokines and adipokines. HGF correlated with proinflammatory cytokines but not with adipokines. The PD-related factors such as RKF, peritoneal property and dialysis glucose load affected levels of proinflammatory cytokines. Body mass index was an important determinant of leptin and adiponectin in PD patients.

Nephropathy associated with contrast medium exposure is a well-known complication of IVP. However, it is uncertain whether iso-osmolar non-iodinated contrast medium (iodixanol) is less nephrotoxic than low-osmolar contrast medium (iohexol).In this single-center, double-blind, prospective study, 50 patients undergoing IVP were randomized into two groups receiving different contrast medium: iodixanol and iohexol. Patients in high risk for contrast nephropathy were included, 28 with renal insufficiency and 19 with diabetes mellitus. We compared the nephrotoxic effect (contrast nephropathy), complement and cytokines profile between the iodixanol and iohexol groups. The mean volume of contrast medium in each IVP procedure was 0.8 mL/kg.The incidence of contrast nephropathy was 4 percent among all patients (one iodixanol and one iohexol). We found no significant differences in contrast nephropathy and allergic reactions between the two groups. There was no significant difference in cytokine profiles in both groups (p0.05).The incidence of allergic reaction was 16 percent among all patients. Twelve percent (3/25) had late reaction after iohexol exposure compared to four percent (2/25) with iodixanol (p = 1.0). One patient had severe skin rash due to late adverse reaction after iodixanol. No mortality was found.New iodixanol and iohexol contrast medium for routine IVP examination are safe and have low nephrotoxicity profile, especially in elderly or high-risk patients. Iodixanol contrast medium has an increased risk to induce severe late adverse reaction compared to iohexol. Allergic reaction may be the main adverse effect after contrast medium infusion.

As an enabling feed/interconnect element for various millimeter wave components, dual polarization quasi-transverse electromagnetic (TEM) waveguides at W-band (75-110 GHz) are investigated with two-dimensional electromagnetic crystal (EMXT) surfaces as the four boundary walls instead of the regular metallic walls. A 2.54 mm x 2.54 mm quasi-TEM square waveguide prototype with a length of 2 mm is fabricated and demonstrated. Both eigenmode and full-wave EM simulations of the prototype verify the quasi-TEM propagation at the designed frequency of 95 GHz with a bandwidth of more than 10% and the low insertion loss for the entire W-band. The prototype waveguide is measured in a WR-10 fixture and the results agree with simulations well. To better understand the loss mechanisms, various design and packaging parameters are studied. Undesirable resonant surface modes have been identified as a critical cause of loss at specific frequencies. This type of waveguides may also be useful for spatial power combining, low loss interconnects, and packaging for millimeter wave systems.

To evaluate the benefits of dialyzer reuse for hemodialysis (HD) patients, including the cost of HD treatment and patient's survival, a comparison was made regarding the standard practice of single-use dialysis.From January 1, 2005, to December 31, 2005, a total of 128,232 successive HD treatments in 822 patients in Chang Gung Memorial Hospital-Kaohsiung Medical Center were included in this study.Approximately 54.25% (446/822) of patients reused dialyzers. The average times of dialyzer reuse was 2.54. The annual hollow fiber cost is reduced by $241,054.08 U.S. dollars (NT $7,834,257.60). The annual cost of hollow fiber was reduced by $540.48 U.S. dollars (NT $17,565.60) in one patient with dialyzer reuse. The mortality rates in dialyzer reuse and single use groups were 3.1% and 10.9% within one year (p0.0001). Multiple logistic regressions showed that single use compared with reuse was associated with higher mortality after adjusting co-morbid conditions including age, diabetes mellitus, etc. CONCLUSIONS. We concluded that the benefits of dialyzer reuse included safety in our center and reduction in cost during a 12-month period. Dialyzer reuse may be a safe alternative.

Despite improvements in renal therapy and technology, the mortality rate of patients with acute renal failure (ARF) remains high. Because ARF is a heterogeneous syndrome, occurring in patients with diverse etiologies and comorbid conditions, predicting its outcome is difficult. This study aims to identify early clinical and laboratory prognostic factors, including acute-phase reactants such as C-reactive protein (CRP), fibrinogen, and albumin, in ARF patients requiring dialysis.From June 2002 to March 2004, 61 patients with ARF requiring dialysis at Chang Gung Memorial Hospital, Chiayi, were prospectively analyzed. For each patient, the worst values of prognostic variables 24 hr before starting dialysis were prospectively assessed.Oliguria, low plasma fibrinogen levels, hypotension, cardiac disease, and neoplastic disease were statistically significant in predicting hospital mortality. Using Youden's index, the best cut-off value for plasma fibrinogen in predicting mortality was 300 mg/dL with a sensitivity and specificity of 61% and 96%, respectively. Serum CRP and serum albumin were not predictive of hospital mortality.Early prognostic factors in predicting mortality for patients with ARF requiring dialysis identified by multivariate logistic regression were oliguria, low plasma fibrinogen, hypotension, cardiac disease, and neoplastic disease. Serum CRP and albumin were not predictive of hospital mortality, whereas a plasma fibrinogen levelor =300 mg/dL had 61% sensitivity and 96% specificity in predicting mortality.

Despite advances in modern technology of dialysis, prognosis of patients with acute renal failure (ARF) remains poor. To give the clinicians the most useful information, a model that accurately predicts outcome early in the course of ARF is required. However, because ARF is a heterogeneous syndrome and occurs in patients with diverse etiologies and some coexisting diseases, predicting outcome early is hard. The aim of this study is to evaluate prospectively the Acute Physiology and Chronic Health Evaluation (APACHE II) and organ system failure (OSF) models, evaluated prior to dialysis, in predicting hospital mortality.From June 2002 to March 2004, ARF patients requiring dialysis at Chang Gung Memorial Hospital, Chiayi, were prospectively recruited for this study. The worst clinical and laboratory data in the 24 hours before initiation of dialysis were prospectively evaluated, and the patients' APACHE II score and OSF number were assessed.A total of 61 patients (40 male and 21 female) were enrolled, of whom 38 (62.3%) died before discharge. By multivariate logistic regression, the APACHE II score (odds ratio 1.3 per increase in one score; P0.001), or OSF number (odds ratio 1.9 per increase in one OSF; P0.01) and oliguria (odds ratio 4.2; P=0.04), were found to be statistically significant prognostic factors for hospital mortality. Mortality increased progressively and significantly as OSF number (chi-square for trend; P=0.001) or the APACHE II score (chi-square for trend; P0.001) increased. By using Youden's index, the best cut-off value for APACHE II was 24, with 63% sensitivity and 96% specificity. The best cut-off value for OSF number was 2, with a sensitivity of 81.6% and a specificity of 60.9%. The areas under the receiver operating characteristic curves for APACHE II and OSF number were 0.847 (95% confidence interval (CI)=0.752-0.942; P0.01) and 0.769 (95% CI=0.646-892; P0.001), respectively, indicating good model discrimination.This study concludes that APACHE II and OSF number measured prior to initiation of dialysis reliably predict outcomes of ARF patients requiring dialysis. The mortality rates increase as the APACHE II score or OSF number increases. For predicting mortality, the APACHE II scoreor = 24 was found to have 63% sensitivity and 96% specificity, and OSF numberor = 2 had 81.6% sensitivity and 60.9% specificity.

Vascular access failure is a major cause of morbidity in chronic hemodialysis (HD) patients. Elevated immunoglobulin-M anticardiolipin antibody (IgM-aCL) titer is associated with stenosis of vascular access in HD patients. The clinical significance of elevated IgM-aCL titer relative to recurrent vascular access thrombosis (VAT) in patients with HD is less clear. However, little information has been available until now about the clinical influence of elevated IgM-aCL titer with recurrent VAT in HD patients from Western countries, and no report exists for Taiwan. This study attempted to determine whether elevated IgM-aCL titer was associated with recurrent VAT in HD patients.This study enrolled 483 patients undergoing HD. IgM-aCL titer and hepatitis C marker were measured for all subjects.Elevated IgM-aCL titer was present in 17.4% (84/483) of patients. There was no association recurrent VAT between elevated and normal IgM-aCL titers (P=0.90). Presence of hepatitis C had significant differences between elevated and normal IgM-aCL titers (P=0.027).We found no significant differences in recurrent VAT between elevated and normal IgM-aCL titer in chronic HD patients. Our results suggest recurrent VAT of synthetic or native fistula may not be caused by elevated IgM-aCL titer in these patients. Presence of hepatitis C may be a cofactor.

While hospitalized for pneumonia with ventilator-dependent respiratory failure, a 45-year-old man on continuous ambulatory peritoneal dialysis (CAPD) had nosocomial peritonitis secondary to infection by expanded spectrum beta-lactamase producing Klebsiella pneumoniae (ESBL-Kp). He was treated successfully with a 3-week course of intraperitoneal (IP) flomoxef therapy without subsequent relapse, loss of peritoneal catheter, ultrafiltration failure, or dialysis inadequacy. The International Consensus Panel recommends IP ceftazidime as the treatment of choice for CAPD patients suffering Klebsiella species-related peritonitis. However, the most appropriate form of IP antibiotic therapy and the outcomes for expanded-spectrum beta-lactamase (ESBL)-producing bacteria-related peritonitis for CAPD patients have not been established yet. Further, the ability to correctly report minimal inhibitory concentrations (MICs) of ceftazidime for ESBL bacteria in the resistant range varies between laboratories, making the diagnosis of ESBL-Kp-related CAPD peritonitis more complex and difficult. Thus, it appears reasonable to suggest that its incidence is probably underestimated and its significance ignored. The authors suggest that a 3-week IP treatment with flomoxef, a synthesized oxacephem, with loading and maintenance doses of 250 and 125 mg/L, respectively, is effective and safe for ESBL-Kp-related peritonitis in these patients. ESBL producing bacterial infection should be considered as a possible cause of overt CAPD-related peritonitis. Early detection of ESBLB pathogens and institution of effective antibiotic treatment may improve the prognosis.

Henoch-Schoenlein purpura (HSP) crescentic glomerulonephritis with acute renal failure in adults is extremely rare. The condition carries a grave renal outcome if it is not appropriately managed. Oral corticosteroids, intravenous methylprednisolone pulse therapy and plasmapheresis with concomitant plasma replacement have been used alone or in various combinations to treat patients with HSP nephritis, yet the effects are uncertain. We describe a 33-year-old man with oliguric acute renal failure in the setting of HSP crescentic glomerulonephritis that is refractory to intravenous methylprednisolone pulse therapy (1,000 mg/day for 3 days) with maintained oral prednisolone (1 mg/kg/day) and oral cyclophosphamide (2 mg/kg/day) for 3 weeks, resulting in successful recovery of renal function after 9 sessions of simple double-filtration plasmapheresis treatment without concomitant plasma replacement. There was no recurrence of vasculitic events within 18 months. In this case, we emphasize that simple double-filtration plasmapheresis without concomitant plasma replacement is an effective and safe modality therapy for adult patients with HSP crescentic glomerulonephritis and acute renal failure, especially when conventional therapy has failed.

Diabetic patients with hemodialysis (HD) have a high mortality rate from atherosclerotic vascular disease (ASVD). However, the extent of the role of hyperhomocystinemia as a risk factor of ASVD is uncertain in diabetic HD patients. We investigated whether there was an association with ASVD events in diabetics and non-diabetics where these were chronic hyperhomocystinemia HD patients.Two hundred patients undergoing HD were included in the study. About 50% of the patients had diabetes mellitus (DM). They had predialysis blood work performed for total homocysteine. A history of DM was elicited using information from the patients' questionnaires and verified by careful inpatient and outpatient chart review.A total of 196 patients had hyperhomocystinemia and were enrolled this study. Mean homocysteine concentration was 29.7 +/- 6.6 micromol/L overall. DM was present in 50.0% of patients. The mean homocysteine concentration was 29.4 +/- 9.5 micromol/L and 29.9 +/- 9.7 micromol/L in diabetic HD patients (n=98) and non-diabetic HD patients (n=98), respectively (P=0.71). There was no association with hyperhomocystinemia between diabetic and non-diabetic in chronic HD patients. There were significant differences including age, sex, HDL cholesterol, triglycerides, hypertension, smoking, serum creatinine, dialysis duration and glucose intolerance in the two groups (P0.05). There were also significant differences in ASVD (P=0.0027) and CVD (P=0.0017) between diabetics and non-diabetics in cases of chronic hyperhomocystinemia HD patients. The adjusted odds ratio for ASVD was 3.02 (95%CI, 1.63 to 5.59) for those subjects with a DM in the highest quartile compared with the lowest 3 quartiles.There were associations with ASVD and CVD in diabetics and non-diabetics in cases of chronic hyperhomocystinemia HD patients. There was no association with hyperhomocystinemia between diabetic and non-diabetic in Taiwanese chronic HD patients. This study found that the presence of DM and advanced age were the major determinants for ASVD events in chronic HD patients, rather than the levels of homocysteine.

PURPOSE: The intracolonic bypass tube has been used both experimentally and clinically to protect the anastomotic site. A newly designed intracolonic bypass, the Valtrac® secured intracolonic bypass, which consisted of a biofragmentable anastomosis ring (BAR) and was connected with a soft, thin vinyl tube, was used in the colon approximately 5 to 10 cm proximal to the anastomotic site. The distal end of the vinyl tube is passed through the colonic anastomosis to the anus to bypass the fecal stream. METHODS: Eighteen piglets were divided into three groups of six each. Group A piglets underwent colon resection and rough anastomosis with large gaps between sutures, followed by Valtrac®-secured intracolonic bypass. Group B piglets underwent the same procedures, but a colonic outlet obstruction also was done with pursestring sutures tied over the anus. Group C piglets underwent colon resection and rough anastomosis, but no intracolonic bypass tube was inserted (as in the control group). RESULTS: All Group A and Group B piglets survived. Passage of the BARs occurred approximately two weeks later. As the barium enema passed through the bypass tube, it showed a patent BAR-secured tube and intact anastomosis with no leakage. In Group C, anastomotic leakage occurred in four of six piglets, three of which died. Barium enema showed leakage at the anastomotic site. CONCLUSIONS: In the animal model we used, our new intracolonic bypass device proved to be a simple, safe, reliable means of protecting the anastomotic site and, thereby, eliminated the need for a diverting colostomy. Still we need further steps to test its potential in clinical use.

Aim: Uremic hyperparathyroidism (UHPT) has been shown to contribute to the development and progression of chronic kidney disease—mineral bone disorder. UHPT is frequently observed in chronic dialysis patients, and patients with UHPT are associated with increased risk of all-cause and cardiovascular mortality. Cinacalcet is a novel agent that increases sensitivity to the calcium-sensing receptor and is approved for control of UHPT. Nevertheless, cinacalcet is costly and information regarding efficacy of low-dose cinacalcet on UHPT is limited. Methods: We conducted a retrospective study to evaluate treatment with either low-dose calcitriol combined with low-dose cinacalcet (25 mg) (d-Cinacalcet) or calcitriol alone (VitD) in dialysis patients with moderate to severe UHPT. A total of 81 dialysis patients were enrolled (40 subjects in d-Cinacalcet group and 41 subjects in VitD group). Demographic data including age, gender, duration on dialysis and biochemical data were reviewed and recorded. Results: At the end of the study, the intact parathyroid hormone (iPTH) levels of the d-Cinacalcet group declined significantly (from 1166.0 ± 469.3 pg/mL to 679.8 ± 421.6 pg/mL, p &lt, 0.0001), while there was no significant change in the VitD group. Significant decrease of serum calcium (Ca: 9.9 ± 0.6 mg/dL vs. 9.6 ± 0.8 mg/dL, p = 0.002), phosphorus (P: 5.9 ± 1.3 mg/dL vs. 4.9 ± 0.9 mg/dL, p &lt, 0.0001) and calcium phosphate product (Ca × P: 58.7 ± 15.0 mg2/dL2 vs. 46.9 ± 8.9 mg2/dL2, p &lt, 0.0001) were observed in the d-Cinacalcet group. In addition, the subjects in the d-Cinacalcet group had a greater proportion to achieve Kidney Disease Outcomes Quality Initiative (KDOQI)-recommended biochemical targets than the subjects in the VitD group (Ca: 48% vs. 24%, P: 78% vs. 32%, Ca × P: 85% vs. 37%, iPTH: 15% vs. 0%). Conclusions: We conclude that combination therapy of low-dose cinacalcet and calcitriol is more effective than calcitriol alone as a treatment for moderate and severe UHPT in chronic dialysis patients. Furthermore, this therapy is associated with improvement in hyperphosphatemia and hypercalcemia.

The stromal cell–derived factor-1 (SDF-1)/CXC receptor 4 (CXCR4) axis plays an important role in tumor angiogenesis and invasiveness in colorectal cancer (CRC) progression. In addition, metastatic CRC remains one of the most difficult human malignancies to treat because of its chemoresistant behavior. However, the mechanism by which correlation occurs between CXCR4 and the clinical response of CRC to chemotherapy remains unknown. We generated chemoresistant cells with increasing doses of oxaliplatin (OXA) and 5-Fluorouracil (5FU) to develop resistance at a clinical dose. We found that the putative markers did not change in the parental cells, but HCT-116/OxR and HCT-116/5-FUR were more aggressive and had higher tumor growth (demonstrated by wound healing, chemotaxis assay, and a nude mice xenograft model) with the use of oxaliplatin. Apoptosis induced by oxaliplatin treatment was significantly decreased in HCT-116/OxR compared to the parental cells. Moreover, HCT-116/OxR cells displayed increased levels of p-gp, p-Akt p-ERK, p-IKBβ, CXCR4, and Bcl-2, but they also significantly inhibited the apoptotic pathways when compared to the parental strain. We evaluated the molecular mechanism governing the signaling pathway associated with anti-apoptosis activity and the aggressive status of chemoresistant cells. Experiments involving specific inhibitors demonstrated that the activation of the pathways associated with CXCR4, ERK1/2 mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K)/Akt is critical to the functioning of the HCT-116/OxR and HCT-116/5-FUR characteristics of chemosensitivity. These findings elucidate the mechanism of CXCR4/PI3K/Akt downstream signaling and provide strategies to inhibit CXCR4 mediated signaling pathway in order to overcome CRC’s resistance to chemotherapy.

Supplemental Digital Content is available in the text, Acute kidney injury (AKI) is a common complication in hospitalized patients. The International Society of Nephrology implemented the “0 by 25” initiative aimed at preventing deaths from treatable AKI worldwide by 2025 and conducted a global snapshot survey in 2014. We joined in the project and conducted this study to compare the epidemiology, risk factors, and prognosis between patients with pure AKI and those with acute-on-chronic kidney disease (ACKD). In this study, we prospectively collected demographic parameters and data on clinical characteristics, baseline comorbidities, management, and outcomes of 201 AKI patients in 18 hospitals in Taiwan from September 2014 to November 2014. The in-hospital mortality rate was 16%. AKI was mostly attributed to sepsis (52%). Multivariate logistic regression indicated that oliguria was a positive independent predictor of in-hospital mortality, whereas preexisting CKD and exposure to nephrotoxic agents were negative independent predictors. The prevalence of vasopressor use, intensive care unit care, and mortality were significantly higher in pure AKI patients than in ACKD patients. Moreover, serum creatinine (SCr) levels significantly increased within 7 days after AKI diagnosis in nonsurvivors but not in survivors in the pure AKI group. By contrast, SCr levels were persistently lower in nonsurvivors than in survivors in the ACKD group during the same period. We thus determined that the prognosis of ACKD patients differed from that of pure AKI patients. Considering the CKD history in the future AKI staging system may improve prognosis prediction.

Background It is well known that the quality of life of patients with chronic kidney disease can be improved by dialysis. While previous studies have used retrospective designs and adhered to a standard target prescribed by clinical guidelines, our study prospectively investigates the association between the adequacy of peritoneal dialysis (PD) and measures of nutritional status on quality-of-life domains in a cohort of incident PD patients. Methods It was a prospective 6-month observational study. Eighty incident PD participants who were treated in a hospital-based PD center were enrolled. The period of enrollment was January 2009–June 2010; follow-up continued until December 2010. PD adequacy indices, including Kt/V urea, weekly Ccr (WCcr), measures of nutritional status (albumin, BMI), and nPCR were measured at 1 month and 6 months after PD initiation. SF-36 health survey questionnaires were used to measure the quality of life. The outcomes were used to measure the changes in the domains of the SF-36 after 6 months of PD therapy. Results Seventy-seven incident patients who underwent PD for 6 months were included in the study. The mean age was 47.3 years, and the male-to-female ratio was 38:39. A peritoneal Kt/V urea value of 1.2, which was also the baseline cutoff value, was found to have the highest influence on SF-36 domains. Patients with baseline peritoneal Kt/V urea value of Limitations A small cohort and a short observation period. Conclusions The baseline level of peritoneal Kt/V urea affected the components of the quality of life after PD initiation. In contrast, a lower baseline nPCR level was associated with deterioration in the quality of life after PD therapy.

Baicalein is the flavonoids with multiple pharmacological activities. The aim of our study was to investigate the effects of baicalein on colorectal cancer (CRC) and to recognize the targets of baicalein treatment. To better understand baicalein's target, proteomic approaches were used to purify and identify the protein substrates using 2D difference gel electrophoresis (2D SDS-PAGE) to elucidate proteins differential display. Results from this study investigate that baicalein treatment of CRC cells results in reduced cell proliferation. As a result, differential protein displays between baicalein-treated and untreated CRC were determined and validated. There were 11 differentially expressed proteins between baicalein-treated and untreated CRC. Furthermore, we demonstrate that baicalein inhibits cancer cell proliferation and reduced reactive oxygen species (ROS) by up-regulating the levels of peroxiredoxin-6 (PRDX6). Knockdown of PRDX6 in baicalein-treated CRC cells by specific small interfering RNA resulted in ROS production and proliferation, opposite of the baicalein treatment scenario as indicated by cell cycle distribution. These results illustrate that baicalein up-regulates the expression of PRDX6, which attenuates the generation of ROS and inhibits the growth of CRC cells, whereas baicalein treatment have no effect on normal epithelial cells.

Protein-bound uremic toxins indoxyl sulfate (IS) and p-cresol sulfate (p-CS) have been implicated as an important factor in uremic syndrome. Recent evidence indicates that both IS and p-CS are predictors of cardiovascular as well as all-cause mortality among chronic dialysis patients. We conducted a study to analyze the relationship between IS and p-CS and vascular access (VA) outcome in chronic hemodialysis (HD) patients.A total of 91 chronic stable HD patients were divided into groups according to survival of VA and frequency of VA dysfunction. Demographic and biochemical data were reviewed and recorded. Serum levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1, and the total and free forms of IS and p-CS were determined.Patients with a history of frequent VA failure and dysfunction had lower albumin and higher levels of ICAM-1, free IS, free and total p-CS. Diabetes was associated with higher IS and p-CS. Logistic regression revealed that diabetes and free p-CS were independent factors associated with poor outcome of VA.Endothelial dysfunction and uremic toxins were associated with survival and function of VA. Diabetes and free p-CS were significantly related to the outcome of VA among chronic HD patients.

Background Entecavir (ETV) is a potent inhibitor of viral replication in chronic hepatitis B. There is no published data concerning ETV therapy in nucleoside analogue (NUC)-naive hepatitis B surface antigen (HBsAg)-positive renal transplant recipients (RTRs). Methods We prospectively treated 27 HBsAg-positive RTRs with ETV since 2007. Serial HBV DNA was assessed at baseline and weeks 12, 24, 52 and 104 after treatment. A cohort of 19 patients who received 2-year lamivudine (3TC) therapy during 2004–2007 was used as a historical control. Results Of the 27 RTRs, 18 (67%) were NUC-naive patients and 9 (33%) were 3TC-experienced without YMDD mutations. HBV DNA levels became undetectable in 70%, 74%, 96% and 100% of patients after 12, 24, 52 and 104 weeks, respectively, of ETV treatment without viral resistance. There was no change of glomerular filtration rate, and no lactic acidosis or myopathy during treatment. By comparison with the 19 3TC-treated patients, ETV-treated RTRs presented higher rates of undetectable HBV DNA than 3TC-treated RTRs (32%, 37%, 63% and 63% at 12, 24, 52 and 104 weeks; PConclusions ETV is effective in treating chronic hepatitis B in RTRs. ETV is safe with regards to renal graft function, lactic acidosis, myopathy and virological resistance.