Histone deacetylase III interactions with BK polyomavirus large tumor antigen may affect protein stability.

BACKGROUND: Human polyomavirus BK (BKPyV) causes associated nephropathy and contributes to urinary tract cancer development in renal transplant recipients. Large tumor antigen (LT) is an early protein essential in the polyomavirus life cycle. Protein acetylation plays a critical role in regulating protein stability, so this study investigated the acetylation of the BKPyV LT protein. METHODS: The BKPyV LT nucleotide was synthesized, and the protein was expressed by transfection into permissive cells. The BKPyV LT protein was immunoprecipitated and subjected to LC-MS/MS analysis to determine the acetylation residues. The relative lysine was then mutated to arginine in the LT nucleotide and BKPyV genome to analyze the role of LT lysine acetylation in the BKPyV life cycle. RESULTS: BKPyV LT acetylation sites were identified at Lys3 and Lys230 by mass spectrometry. HDAC3 and HDAC8 and their deacetylation activity are required for BKPyV LT expression. In addition, mutations of Lys3 and Lys230 to arginine increased LT expression, and the interaction of HDAC3 and LT was confirmed by coimmunoprecipitation. CONCLUSIONS: HDAC3 is a newly identified protein that interacts with BKPyV LT, and LT acetylation plays a vital role in the BKPyV life cycle.

DNA Methylation of Window of Implantation Genes in Cervical Secretions Predicts Ongoing Pregnancy in Infertility Treatment.

Window of implantation (WOI) genes have been comprehensively identified at the single cell level. DNA methylation changes in cervical secretions are associated with in vitro fertilization embryo transfer (IVF-ET) outcomes. Using a machine learning (ML) approach, we aimed to determine which methylation changes in WOI genes from cervical secretions best predict ongoing pregnancy during embryo transfer. A total of 2708 promoter probes were extracted from mid-secretory phase cervical secretion methylomic profiles for 158 WOI genes, and 152 differentially methylated probes (DMPs) were selected. Fifteen DMPs in 14 genes (BMP2, CTSA, DEFB1, GRN, MTF1, SERPINE1, SERPINE2, SFRP1, STAT3, TAGLN2, TCF4, THBS1, ZBTB20, ZNF292) were identified as the most relevant to ongoing pregnancy status. These 15 DMPs yielded accuracy rates of 83.53%, 85.26%, 85.78%, and 76.44%, and areas under the receiver operating characteristic curves (AUCs) of 0.90, 0.91, 0.89, and 0.86 for prediction by random forest (RF), naïve Bayes (NB), support vector machine (SVM), and k-nearest neighbors (KNN), respectively. SERPINE1, SERPINE2, and TAGLN2 maintained their methylation difference trends in an independent set of cervical secretion samples, resulting in accuracy rates of 71.46%, 80.06%, 80.72%, and 80.68%, and AUCs of 0.79, 0.84, 0.83, and 0.82 for prediction by RF, NB, SVM, and KNN, respectively. Our findings demonstrate that methylation changes in WOI genes detected noninvasively from cervical secretions are potential markers for predicting IVF-ET outcomes. Further studies of cervical secretion of DNA methylation markers may provide a novel approach for precision embryo transfer.

In Vitro and In Vivo Assessments of Anti-Hyperglycemic Properties of Soybean Residue Fermented with Rhizopus oligosporus and Lactiplantibacillus plantarum.

Soy isoflavones possess antioxidative, anti-inflammatory, anti-diabetic and phytoestrogenic properties. Soybean residue contains a fair amount of nutrients such as glycosylated isoflavones, minerals and dietary fibers, and is a substantial waste product produced from soymilk and tofu manufacturing. A solid-state fermentation of soybean residue by Rhizopus oligosporus or co-inoculated with Lactiplantibacillus plantarum improves the availability of isoflavones and GABA content which is attributed to ameliorated hyperglycemic symptoms in STZ-induced hyperglycemic mice. The effortless solid-state fermentation with present microbial manipulation supports an anti-hyperglycemia value-added application of soybean residue for functional food development. Background: Due to an awareness of the food crisis and with a rapidly rising prevalence of diabetes, recycling the substantial fibrous soybean residue disposed from soy industries has received consideration. Methods: Lactiplantibacillus plantarum was previously screened for active glutamate decarboxylase, and ß-glucosidase activities were adopted for the fermenting of soybean residue using a traditional tempeh solid-state fermenting process with fungal Rhizopus oligosporus. Fermented soybean residue was chemically analyzed and functionally assessed in in vitro and in vivo hyperglycemic conditions. Results: A 48 h longer solid-state fermentation of the soybean residue co-inoculated with R. oligosporus and L. plantarum showed improved contents of isoflavone aglycones and GABA which were attributed to augmented antioxidative capacity, lowered ROS level, improved blood biochemistry, and better blood glucose homeostasis in STZ-induced hyperglycemic mice. Conclusion: The advantages of a food industrial effortless fermentation process, and a health nutritional endorsing anti-hyperglycemic value-added property offer a practical alternative in recycled soybean residue.

Statin Therapy for Hyperlipidemic Patients With Chronic Kidney Disease and End-Stage Renal Disease: A Retrospective Cohort Study Based on 925,418 Adults in Taiwan.

Background: For non-dialysis patients with hyperlipidemia, statins may provide clinical benefits in reducing mortality risk; however, the optimal treatment for dialysis patients with hyperlipidemia remains debatable. We evaluated the mortality risks for hyperlipidemic patients with renal disorders associated with statin therapy (ST), using the insurance claims data of Taiwan. Methods: From hyperlipidemic patients diagnosed in 2000-2011, we identified 555,153 patients receiving statin treatment for at least 90 days continuously and 1,141,901 non-statin users, and then randomly selected, from both groups, the propensity score-matched subcohorts of statin users and nonusers in a 1:1 pair by renal function: 415,453 pairs with normal renal function , 43,632 pairs with chronic kidney disease (CKD), and 3,624 pairs with end-stage renal disease (ESRD). We compared the mortalities, by the end of 2016, from all causes, cancer, heart disease, and septicemia between statin users and non-users and between hydrophilic-statin users and lipophilic-statin users. The Cox method estimated ST users to non-user hazard ratios. The time-dependent model was also conducted as sensitivity analysis. Results: The mean ages were 58.7 ± 10.7, 64.2 ± 10.7, and 62.2 ± 10.8 years in normal renal function, CKD, and ESRD groups, respectively. Compared with non-users, statin users had reduced mortality risks from all causes for 32%-38%, from cancer for 37%-46%, from heart disease for 6%-24%, and from septicemia for 17%-21% in all three renal groups. The hydrophilic statin therapy was superior than the lipophilic statin therapy, particularly for reducing deaths from all-causes and cancer. The results under the time-dependent model were similar. Conclusion: Statin therapy is associated with reduced all-causes and non-cardiovascular mortality in ESRD patients.

Statins Reduce Hepatocellular Carcinoma Risk in Patients with Chronic Kidney Disease and End-Stage Renal Disease: A 17-Year Longitudinal Study.

Hepatocellular carcinoma (HCC) is the most common cancer in end-stage renal disease (ESRD) patients in Taiwan. Whether statin therapy associated with the HCC risk in hyperlipidemic patients with chronic kidney disease (CKD) and ESRD is unclear. Using population-based insurance claim data from Taiwan, we identified from hyperlipidemic patients taking statins or not (677,364 versus 867,707) in 1999-2015. Among them, three pairs of propensity score matched statin and non-statin cohorts were established by renal function: 413,867 pairs with normal renal function (NRF), 46,851 pairs with CKD and 6372 pairs with ESRD. Incidence rates of HCC were compared, by the end of 2016, between statin and non-statin cohorts, between hydrophilic statins (HS) and lipophilic statins (LS) users, and between statin-ezetimibe combination therapy (SECT) and statin monotherapy (SM) users. The HCC incidence increased progressively from NRF to CKD and ESRD groups, was lower in the statin cohort than in the non-statin cohort, with the differences of incidence per 10,000 person-years increased from (7.77 vs. 21.4) in NRF group to (15.8 vs. 37.1) in CKD group to (19.1 vs. 47.8) in ESRD group. The incidence increased with age, but the Cox method estimated hazard ratios showed a greater statin effectiveness in older patients. Among statin users, the HCC incidence was lower in HS users than in LS users, and lower in SECT users than in SM users, but the difference was significant only in the NRF group. Hyperlipidemic patients with CKD and ESRD receiving statins are at reduced HCC risks; the treatment effectiveness is superior for HS users than for LS users, and for SECT users than for SM users, but not significant.

Secular trends in the incidence of fracture hospitalization between 2000 and 2015 among the middle-aged and elderly persons in Taiwan: A nationwide register-based cohort study.

OBJECTIVE: Fractures are a common reason for hospital admissions. However, regional and short-term studies show a varying incidence rate (IR) of fractures, and most of the surveys were conducted from only a few medical centers. Therefore, this study aims to investigate the epidemiological data of fracture hospitalizations of middle-aged and elderly persons in Taiwan between 2000 and 2015. MATERIALS AND METHODS: Data from fractures occurring between 2000 and 2015 were obtained from the National Health Insurance Research Database in Taiwan for this study. The IR of fracture admission in patients, aged 40 years or older at the time of admission and first-time diagnosed with a fracture following admission, was calculated. RESULTS: We found that the IR of the fracture hospitalizations declined considerably from 95.70 per 10,000 person-years in 2000, to 68.48 per 10,000 person-years in 2015. The three most common fracture hospitalizations accounting for more than 50% of all fractures were fractures of the femur/hip, radius or ulna, and vertebral column. The IR of fracture hospitalization increased with age and was found to be higher in women than in men. The most common cause of fracture hospitalization for men and patients under 65 years of age was traffic accidents. In contrast, falls were the most frequent causes of fracture hospitalization for women and patients over 65 years of age. CONCLUSION: The present study furnishes an updated picture of the incidence of fracture hospitalization over a 16-year period among middle-aged and elderly persons in Taiwan.

Influence of Admission Time on Health Care Quality and Utilization in Patients with Stroke: Analysis for a Possible July Effect and Weekend Effect.

(1) Purpose: Undesirable health care outcomes could conceivably increase as a result of the entry of new, less experienced health care personnel into patient care during the month of July (the July effect) or as a result of the less balanced allocation of health care resources on weekends (the weekend effect). Whether these two effects were present in Taiwan's National Health Insurance (NHI) system was investigated. (2) Methods: The current study data were acquired from the NHI Research Database. The research sample comprised ≥18-year-old patients diagnosed as having a stroke for the first time from 1 January 2006 to 30 September 2012. The mortality rate within 30 days after hospitalization and readmission rate within 14 days after hospital discharge were used as health care quality indicators, whereas health care utilization indicators were the total length and cost of initial hospitalization. (3) Results: The results revealed no sample-wide July effect with regard to the four indicators among patients with stroke. However, an unexpected July effect was present among in-patients in regional and public hospitals, in which the total lengths and costs of initial hospitalization for non-July admissions were higher than those for July admissions. Furthermore, the total hospitalization length for weekend admissions was 1.06-1.07 times higher than that for non-weekend admissions; the total hospitalization length for weekend admissions was also higher than that for weekday admissions during non-July months. Thus, weekend admission did not affect the health care quality of patients with stroke but extended their total hospitalization length. (4) Conclusions: Consistent with the NHI's general effectiveness in ensuring fair, universally accessible, and high-quality health care services in Taiwan, the health care quality of patients examined in this study did not vary significantly overall between July and non-July months. However, a longer hospitalization length was observed for weekend admissions, possibly due to limitations in personnel and resource allocations during weekends. These results highlight the health care efficiency of hospitals during weekends as an area for further improvement.

Epidemiological characteristics of diabetic kidney disease in Taiwan.

Diabetic kidney disease (DKD) is a critical microvascular complication of diabetes. With the continuous increase in the prevalence of diabetes since 2000, the prevalence of DKD has also been increasing in past years. The prevalence of DKD among individuals with type 2 diabetes in Taiwan increased from 13.32% in 2000 to 17.92% in 2014. The cumulative incidence of DKD among individuals with type 1 diabetes in Taiwan was higher than 30% during 1999-2012. DKD is the leading cause of end-stage renal disease (ESRD), with a prevalence of approximately 45% in a population on chronic dialysis in Taiwan. Among individuals with type 2 diabetes, the prevalence of ESRD in the receipt of dialysis also increased from 1.32% in 2005 to 1.47% in 2014. Risk factors for DKD development are age, race, family history, hyperglycemia, hypertension, dyslipidemia, dietary patterns, and lifestyles. Prognostic factors that aggravate DKD progression include age, family history, sex, glycemic control, blood pressure (BP), microvascular complications, and atherosclerosis. This review summarizes updated information on the onset and progression of DKD, particularly in the Taiwanese population. Translating these epidemiological features is essential to optimizing the kidney care and improving the prognosis of DKD in Asian populations.

Secular trends of patients hospitalized for major osteoporotic fractures based on a national claims database.

There was a reduction in the hospitalization rate for major osteoporotic fractures. As per our analysis, hospitalization for site-specific fractures showed a declining trend for hip and vertebral fractures for both the sexes. However, an increasing trend was noted in women regarding hospitalization for forearm fracture. PURPOSE: Major osteoporotic fractures (MOFs) constitute a large proportion of the total expenditures for public healthcare. Knowing the secular trends of MOF will allow for more efficient use of healthcare resources, but such data are insufficient for the current population of Taiwan. Therefore, we investigated the epidemiological data of MOF hospitalization from adults 50 years of age or older in Taiwan during the period 2000-2015. METHODS: The data analyzed were acquired from the Taiwan National Health Insurance Research Database (NHIRD) entries between 2000 and 2015. All study subjects were 50 years of age or older at the time of admission and diagnosed as having MOF. RESULTS: A general decline was observed in the incidence rate (IR) of MOF hospitalization for the whole population, from 74.52 per 10,000 person-years (PYs) in 2000 to 55.19 in 2015. Females aged ≥65 years had the highest rates of hospitalization for MOF among the subgroups analyzed. Apart from the wrist fracture hospitalization rates in both sexes, which remained steady, all other site-specific fracture hospitalization rates exponentially increased with age. Among men, the IRs of all MOF hospitalization were steady, except for a slight decrease in hip and vertebral fracture hospitalizations. In women, hip and vertebral fracture hospitalization rates gradually decreased, humerus and wrist fracture hospitalization remained steady, and forearm fracture hospitalization increased. CONCLUSIONS: Hospitalization rates of MOF decreased. The trend of site-specific fracture hospitalization analysis showed that hip and vertebral fractures decreased for both sexes. However, an increasing trend in forearm fracture hospitalization was noticed among females.

The Cancer Risk among Physicians in Taiwan, a Population-Based Propensity Score Matched Cohort Study.

BACKGROUND: The field of physician health is gaining increasing attention; however, most research and interventions have concentrated on factors such as job stress, mental health, and substance abuse. The risks of major cancers in physicians remain unclear. We used a propensity score-matched analysis to investigate the risk of cancer in physicians relative to the general population who had no healthcare-related professional background. METHODS: Data were obtained from the National Health Insurance system in Taiwan. The physician cohort contained 29,713 physicians, and each physician was propensity score-matched with a person from the general population. RESULTS: The physicians demonstrated a 0.90-fold lower risk of all-cancers (95% confidence interval [CI] = 0.83 - 0.96) when compared with the general population. Female physicians had a higher risk of cancer than male physicians (adjusted hazard ratio [HR] = 1.59; 95% CI = 1.28 - 1.96). Physicians had higher risks of prostate (HR = 1.26; 95% CI = 1.00 - 1.59) and thyroid cancers (HR = 3.16; 95% CI = 1.69 - 5.90) when compared with the general population. CONCLUSION: Physicians have lower rates of overall cancer risk than the general population. Female physicians have higher cancer risks than male physicians. Male physicians have higher risks of thyroid and prostate cancer relative to the general population.

Peptic Ulcer Disease is Associated with Increased Risk of Chronic Urticaria Independent of Helicobacter pylori Infection: A Population-Based Cohort Study.

BACKGROUND: Some studies showed patients with chronic urticaria have a higher rate of peptic ulcer disease (PUD). Whether PUD is a risk factor for chronic urticaria is unclear. OBJECTIVE: The objective of this study was to evaluate the incidence of and risk factors for chronic urticaria in patients with PUD using the Taiwan National Health Insurance Research Database. METHODS: We conducted a retrospective nationwide cohort study of the period 2000-2012 and involving 11,901 patients with PUD who underwent Helicobacter pylori (HP) therapy (PUD + HP group) and an equal number of matched patients without HP infection (PUD - HP group). Furthermore, we enrolled 23,802 patients without PUD for comparison (non-PUD group). The Cox proportional hazards regression model was used to analyze chronic urticaria risk after adjusting for potential confounding factors. RESULTS: The mean ages of the three groups were around 50 years. Approximately 42.6% were female. Chronic urticaria incidences in the PUD + HP and PUD - HP groups were both significantly higher than that in the non-PUD group. The hazard ratios of chronic urticaria in the PUD + HP group and the PUD - HP group were 1.34 (95% confidence interval 1.09-1.64) and 1.45 (95% confidence interval 1.19-1.79), respectively. The risk difference became significant 2 years after patients with PUD had the HP infection tests and persisted till the end of follow-up. The risk increase was significant in patients with PUD who were female or aged 40-64 years. There was no difference in the risk comparison between PUD + HP and PUD - HP groups. CONCLUSIONS: Peptic ulcer disease, independent of HP infection, is associated with an increased chronic urticaria risk. Patients with PUD who were female or aged 40-64 years are more likely to have chronic urticaria.

Efficacy of aspirin, clopidogrel, and ticlopidine in stroke prevention: A population-based case-cohort study in Taiwan.

BACKGROUND: In real-world practice settings, there is insufficient evidence on the efficacy of antiplatelet drugs, including clopidogrel, aspirin, and ticlopidine, in stroke prevention. PURPOSE: To compare the efficacies between aspirin and clopidogrel and aspirin and ticlopidine in stroke prevention. METHODS: This population-based case-cohort study utilized the data obtained from a randomized sample of one million subjects in the Taiwan National Health Insurance Research Database. Patients who were hospitalized owing to the primary diagnosis of ischemic stroke from January 1, 2000 to December 31, 2010 and treated with aspirin, ticlopidine, or clopidogrel were included in the study. Propensity score matching with a 1:4 ratio was performed to compare aspirin with ticlopidine and clopidogrel. The criteria for inclusion were the use of one of the three antiplatelet drugs for more than 14 days within the first month after the stroke and then continued use of the antiplatelet drugs until the study endpoint of recurrent stroke. RESULTS: During the 3-year follow-up period, the recurrent stroke rates were 1.62% (42/2585), 1.48% (3/203), and 2.55% (8/314) in the aspirin, ticlopidine, and clopidogrel groups, respectively. Compared with the patients treated with aspirin, those treated with clopidogrel and ticlopidine showed competing risk-adjusted hazard ratios of recurrent stroke of 2.27 (1.02-5.07) and 0.62 (0.08-4.86), respectively. CONCLUSION: Compared with the patients treated with aspirin, those treated with clopidogrel were at a higher risk of recurrent stroke. For stroke prevention, aspirin was superior to clopidogrel whereas ticlopidine was not inferior to aspirin.

Older Age and High Serum Ferritin Levels Associated With the Risk of Chronic Cytopenia in Hemodialysis Patients.

Leukopenia or thrombocytopenia is sometimes observed in end-stage renal disease (ESRD) patients, but the association between chronic leukopenia or thrombocytopenia and hemodialysis (HD) is still unclear. We aimed to investigate the incidence of chronic leukopenia or thrombocytopenia in patients with ESRD who received HD and to determine the risk factors of this complication. We retrospectively analyzed ESRD patients treated with HD at Ditmanson Medical Foundation Chia-Yi Christian Hospital in 2018. The risk factors for the occurrence of chronic leukopenia and thrombocytopenia were analyzed by Cox regression models. Of the 473 patients in our study cohort, 46 (9.7%) patients had a hematologic abnormality, including 18 patients with chronic leukopenia, 18 with chronic thrombocytopenia, and 10 with pancytopenia. Multivariate analysis revealed that patient age ≥60 years at the initiation of dialysis was a significant predictor for both chronic leukopenia [adjusted hazard ratio (aHR), 2.71; 95% confidence interval (CI), 1.06-6.89] and chronic thrombocytopenia (aHR, 2.83; 95% CI, 1.08-7.35). Chronic liver disease (aHR, 3.31; 95% CI, 1.27-8.61) and serum ferritin levels >800 mg/dl (aHR, 3.29; 95% CI, 1.29-8.39) were risk factors for chronic thrombocytopenia. A trend showed that vitamin D from intravenous supplementation (aHR, 0.13; 95% CI, 0.01-1.16, P = 0.066) and serum phosphorous level (aHR, 0.73; 95% CI, 0.53-1.02, P = 0.068) may be associated with chronic thrombocytopenia. Our study demonstrated that hematological abnormality was a long-term complication of HD. These results reveal that older patients with HD and high serum ferritin levels are at an elevated risk for chronic cytopenia. Healthcare professionals should be aware of this risk when treating HD patients in order to improve their prognosis.

Functional Gene Clusters in Global Pathogenesis of Clear Cell Carcinoma of the Ovary Discovered by Integrated Analysis of Transcriptomes.

Clear cell carcinoma of the ovary (ovarian clear cell carcinoma (OCCC)) is one epithelial ovarian carcinoma that is known to have a poor prognosis and a tendency for being refractory to treatment due to unclear pathogenesis. Published investigations of OCCC have mainly focused only on individual genes and lack of systematic integrated research to analyze the pathogenesis of OCCC in a genome-wide perspective. Thus, we conducted an integrated analysis using transcriptome datasets from a public domain database to determine genes that may be implicated in the pathogenesis involved in OCCC carcinogenesis. We used the data obtained from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) DataSets. We found six interactive functional gene clusters in the pathogenesis network of OCCC, including ribosomal protein, eukaryotic translation initiation factors, lactate, prostaglandin, proteasome, and insulin-like growth factor. This finding from our integrated analysis affords us a global understanding of the interactive network of OCCC pathogenesis.

Increased risk of developing peripheral artery disease in hemodialysis patients receiving statin treatments: a population-based cohort study in Taiwan.

BACKGROUND: Few investigations have evaluated the influences on peripheral arterial disease (PAD) risk of statin treatment in hemodialysis (HD) subjects with hyperlipidemia (HL). METHODS: From the National Health Insurance Research Dataset, we identified 3658 HD patients with statin therapy for HL as the statin cohort, and then selected, by 1:1 propensity score matching, 3658 HD patients with HL but without statin use as the nonstatin cohort in 2000-07. The cohorts were followed through until the end of 2011. We used Cox proportional hazards regression analysis to assess the hazard ratio (HR) of PAD development. RESULTS: The average follow-up period was 4.18 years; the incident PAD risk was 1.35-fold greater in statin users than in nonusers (16.87 versus 12.46/1000 person-years), with an adjusted HR (aHR) of 1.34 for PAD [95% confidence interval (CI) 1.12-1.62]. The PAD risk increases were significant for patients receiving fluvastatin (aHR 1.88; 95% CI 1.12-3.14) and atorvastatin (aHR 1.60; 95% CI 1.24-2.08). The risk increased with higher annual average statin dosage (P for trend <0.0001); the risk was higher for those receiving moderate-intensity statin treatment. The sensitivity test revealed similar findings. CONCLUSIONS: HD patients with HL on statin medication were at increased PAD risk, which increased with cumulative statin dosage. Thorough considerations are needed before prescribing statins to HD patients.

Prehemodialysis arteriovenous access creation is associated with better cardiovascular outcomes in patients receiving hemodialysis: a population-based cohort study.

BACKGROUND: Cardiovascular (CV) disease contributes to nearly half of the mortalities in patients with end-stage renal disease. Patients who received prehemodialysis arteriovenous access (pre-HD AVA) creation had divergent CV outcomes. METHODS: We conducted a population-based cohort study by recruiting incident patients receiving HD from 2001 to 2012 from the Taiwan National Health Insurance Research Database. Patients' characteristics, comorbidities, and medicines were analyzed. The primary outcome of interest was major adverse cardiovascular events (MACEs), defined as hospitalization due to acute myocardial infarction, stroke, or congestive heart failure (CHF) occurring within the first year of HD. Secondary outcomes included MACE-related mortality and all-cause mortality in the same follow-up period. RESULTS: The patients in the pre-HD AVA group were younger, had a lower burden of underlying diseases, were more likely to use erythropoiesis-stimulating agents but less likely to use renin-angiotensin-aldosterone system blockers. The patients with pre-HD AVA creation had a marginally lower rate of MACEs but a significant 35% lower rate of CHF hospitalization than those without creation (adjusted hazard ratio (HR) 0.65, 95% confidence interval (CI) [0.48-0.88]). In addition, the pre-HD AVA group exhibited an insignificantly lower rate of MACE-related mortality but a significantly 52% lower rate of all-cause mortality than the non-pre-HD AVA group (adjusted HR 0.48, 95% CI [0.39-0.59]). Sensitivity analyses obtained consistent results. CONCLUSIONS: Pre-HD AVA creation is associated with a lower rate of CHF hospitalization and overall death in the first year of dialysis.

The uremic toxin p-cresol promotes the invasion and migration on carcinoma cells via Ras and mTOR signaling.

P-cresol (PC) shows toxic effects on a variety of cells such as renal proximal tubular cells, glomerular mesangial cells, vascular smooth muscle cells, vascular endothelial cells, cardiomyocytes, cardiac fibroblasts, monocytes, osteoblasts and osteoclasts. The molecular mechanism and role of PC in the progression of urothelial carcinoma have not been documented. To understand the impact of PC on bladder cancer progression, human bladder cancer TSGH8301 cells were treated PC with various concentration (25-100 µM). MTT assay revealed the toxicity of PC on TSGH8301 cells dose-dependently. MMP-2 and MMP-9 expressions of the PC-treated cells were enhanced by using gelatin zymography. The wound healing assay and transwell migration analysis were performed to assay the migratory and invasive effects of PC on TSGH8301 cell and the migrated cell numbers were markedly increased by PC treatment. Moreover, we further detected the expression of Ras, PI3K and Akt proteins that involved in the invasion/migration of the cancer. Inhibiting the Ras and mTOR signaling pathways by Y27632 or/and everolimus improved cancer cell progression induced by PC. This study may clarify the impact of PC on migration and invasion of carcinoma cells.