Altered CD226/TIGIT expressions were associated with NK phenotypes in primary antiphospholipid syndrome and affected by IL-4/JAK pathway.

Natural killer (NK) cells were reported to be involved in the pathogenesis of primary antiphospholipid syndrome (pAPS). Immunosuppressive receptor T-cell immunoreceptor with Ig and ITIM domains (TIGIT) and activating receptor cluster of differentiation 226 (CD226) are specifically expressed on NK cells with competitive functions. This study aims to investigate the expression diversities of CD226/TIGIT on NK subsets and their associations with NK subsets activation phenotypes and potential clinical significance, furthermore, to explore potential cause for CD226/TIGIT expression diversities in pAPS. We comparatively assessed the changes of CD56brightNK, CD56dimNK, and NK-like cells in 70 pAPS patients compared with control groups, including systemic lupus erythematosus, asymptomatic antiphospholipid antibodies carriers (asymp-aPLs carriers), and healthy controls and their expression diversities of CD226/TIGIT by flow cytometry. CD25, CD69, CD107α expression, and interferon gamma (IFN-γ) secretion levels of NK subsets were detected to determine the potential association of CD226/TIGIT expression with NK subsets phenotypes. CD226/TIGIT expression levels were compared among different subgroups divided by aPLs status. Moreover, in vitro cultures were conducted to explore the potential mechanisms of CD226/TIGIT expression imbalance. CD56brightNK and CD3+CD56+NK-like cells were significantly increased while CD56dimNK cells were obviously decreased in pAPS, and CD56brightNK and NK-like cells exhibited significantly higher CD226 but lower TIGIT expressions. CD226+CD56brightNK and TIGIT-CD56brightNK cells show higher CD69 expression and IFN-γ secretion capacity, and CD226+NK-like and TIGIT-NK-like cells showed higher expressions of CD25 and CD69 but lower apoptosis rate than CD226- and TIGIT+CD56brightNK/NK-like cells, respectively. The imbalanced CD226/TIGIT expressions were most significant in aPLs triple-positive group. Imbalanced expressions of CD226/TIGIT on CD56brightNK and NK-like cells were aggravated after interleukin-4 (IL-4) stimulation and recovered after tofacitinib blocking. Our data revealed significant imbalanced CD226/TIGIT expressions on NK subsets in pAPS, which closely associated with NK subsets phenotypes and more complicated autoantibody status. CD226/TIGIT imbalanced may be affected by IL-4/Janus Kinase (JAK) pathway activation.

Digital health interventions to promote healthy lifestyle in hemodialysis patients: an interventional pilot study.

Low physical activity has been associated with poor prognosis in hemodialysis (HD) patients. Interventions to maintain healthy lifestyle in this population are important to reduce mortality. This study aimed to evaluate the effectiveness of digital health interventions (DHIs) for improving the physical activity and health-related quality of life (HRQoL) in HD patients. The 24-week prospective study enrolled 31 clinically stable HD patients. All participants were assigned home exercises and provided with wearable devices. Dietary and exercise information was uploaded to a health management platform. Suggestions about diet and exercise were provided, and a social media group was created. Physical performance testing was performed at baseline and during weeks 4, 8, 12, 16 and 24. HRQoL and nutritional status were evaluated. A total of 25 participants completed the study. After the interventions, the daily step count increased 1658 steps. The 10-time-repeated sit-to-stand test reduced by 4.4 s, the sit-to-stand transfers in 60 s increased 12 repetitions, the distance of six-minute walk test (6MWT) increased by 55.4 m. The mental health components and burden of kidney disease of the Kidney Disease Quality of Life survey, and subjective global assessment (SGA) scores improved. By Spearman correlation, the monthly step count correlated positively with 6MWT and SGA. DHIs that combined wearable devices, a health management platform, and social media could strengthen physical activity and improve the HRQoL and nutrition of maintenance HD patients. The results outline a new model to promote healthy lifestyle behaviors in HD patients.

25-Hydroxy vitamin D deficiency is an inferior predictor of peripheral T-cell lymphomas.

The aim of the study was to explore the significance and prognostic value of 25-hydroxy vitamin D (25-(OH) D) deficiency in peripheral T-cell lymphomas (PTCLs). One hundred fifty-six patients of newly diagnosed PTCLs were enrolled in the study. Univariate and multivariate regression analyses were performed to determine independent risk factors for progression-free survival (PFS) and overall survival (OS). Receiver operating characteristic (ROC) curves were plotted, and corresponding areas under the curve (AUC) were calculated to estimate the accuracy of International Prognostic Index (IPI) plus 25-(OH) D deficiency and Prognostic Index for T-cell lymphoma (PIT) plus 25-(OH) D deficiency respectively in PTCL risk stratification. Our results showed that the 25-(OH) D deficiency was an independent inferior prognostic factor for both PFS (P = 0.0019) and OS (P = 0.005) for PTCLs, especially for AITL and PTCL-not otherwise specified (PTCL-NOS). Additionally, adding 25-(OH) D deficiency to PIT indeed has a superior prognostic significance than PIT alone for PFS (P = 0.043) and OS (P = 0.036). Multivariate COX regression analysis revealed that PIT 2‒4, albumin (ALB) ≤ 35 g/L, and 25-(OH) D deficiency were regarded as independent risk factors of PFS and OS. Our results showed that 25-(OH) D deficiency was associated with inferior survival outcome of PTCLs, especially for AITL and PTCL-NOS. PIT plus 25-(OH) D deficiency could better indicate the prognosis for PFS and OS of PTCLs than PIT.

Roux-en-Y and One-Anastomosis Gastric Bypass Surgery Are Superior to Sleeve Gastrectomy in Lowering Glucose and Cholesterol Levels Independent of Weight Loss: a Propensity-Score Weighting Analysis.

BACKGROUND: The superior effects of gastric bypass surgery in preventing cardiovascular diseases compared with sleeve gastrectomy are well-established. However, whether these effects are independent of weight loss is not known. METHODS: In this retrospective cohort study, we compared the change in cardiometabolic risks of 1073 diabetic patients undergoing Roux-en-Y gastric bypass (RYGB) (n = 265), one-anastomosis gastric bypass (OAGB) (n = 619), and sleeve gastrectomy (SG) (n = 189) with equivalent weight loss from the Min-Shen General Hospital. Propensity score-weighting, multivariate regression, and matching were performed to adjust for baseline differences. RESULTS: After 12 months, OAGB and, to a lesser extent, RYGB exhibited superior effects on glycemic control compared with SG in patients with equivalent weight loss. The effect was significant in patients with mild-to-modest BMI reduction but diminished in patients with severe BMI reduction. RYGB and OAGB had significantly greater effects in lowering total and low-density lipoprotein cholesterol than SG, regardless of weight loss. The results of matching patients with equivalent weight loss yielded similar results. The longer length of bypassed biliopancreatic (BP) limbs was correlated with a greater decrease in glycemic levels, insulin resistance index, lipids, C-reactive protein (CRP) levels, and creatinine levels in patients receiving RYBG. It was correlated with greater decreases in BMI, fasting insulin, insulin resistance index, and C-reactive protein levels in patients receiving OAGB. CONCLUSION: Diabetic patients receiving OAGB and RYGB had lower glucose and cholesterol levels compared with SG independent of weight loss. Our results suggest diabetic patients with cardiovascular risk factors such as hypercholesterolemia to receive bypass surgery.

Genome-Wide Association Studies for Albuminuria of Nondiabetic Taiwanese Population.

INTRODUCTION: Chronic kidney disease, which is defined by a reduced estimated glomerular filtration rate and albuminuria, imposes a large health burden worldwide. Ethnicity-specific associations are frequently observed in genome-wide association studies (GWAS). This study conducts a GWAS of albuminuria in the nondiabetic population of Taiwan. METHODS: Nondiabetic individuals aged 30-70 years without a history of cancer were enrolled from the Taiwan Biobank. A total of 6,768 subjects were subjected to a spot urine examination. After quality control using PLINK and imputation using SHAPEIT and IMPUTE2, a total of 3,638,350 single-nucleotide polymorphisms (SNPs) remained for testing. SNPs with a minor allele frequency of less than 0.1% were excluded. Linear regression was used to determine the relationship between SNPs and log urine albumin-to-creatinine ratio. RESULTS: Six suggestive loci are identified in or near the FCRL3 (p = 2.56 × 10-6), TMEM161 (p = 4.43 × 10-6), EFCAB1 (p = 2.03 × 10-6), ELMOD1 (p = 2.97 × 10-6), RYR3 (p = 1.34 × 10-6), and PIEZO2 (p = 2.19 × 10-7). Genetic variants in the FCRL3 gene that encode a secretory IgA receptor are found to be associated with IgA nephropathy, which can manifest as proteinuria. The PIEZO2 gene encodes a sensor for mechanical forces in mesangial cells and renin-producing cells. Five SNPs with a p-value between 5 × 10-6 and 5 × 10-5 are also identified in five genes that may have a biological role in the development of albuminuria. CONCLUSION: Five new loci and one known suggestive locus for albuminuria are identified in the nondiabetic Taiwanese population.

ER ribosomal-binding protein 1 regulates blood pressure and potassium homeostasis by modulating intracellular renin trafficking.

BACKGROUND: Genome-wide association studies (GWASs) have linked RRBP1 (ribosomal-binding protein 1) genetic variants to atherosclerotic cardiovascular diseases and serum lipoprotein levels. However, how RRBP1 regulates blood pressure is unknown. METHODS: To identify genetic variants associated with blood pressure, we performed a genome-wide linkage analysis with regional fine mapping in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) cohort. We further investigated the role of the RRBP1 gene using a transgenic mouse model and a human cell model. RESULTS: In the SAPPHIRe cohort, we discovered that genetic variants of the RRBP1 gene were associated with blood pressure variation, which was confirmed by other GWASs for blood pressure. Rrbp1- knockout (KO) mice had lower blood pressure and were more likely to die suddenly from severe hyperkalemia caused by phenotypically hyporeninemic hypoaldosteronism than wild-type controls. The survival of Rrbp1-KO mice significantly decreased under high potassium intake due to lethal hyperkalemia-induced arrhythmia and persistent hypoaldosteronism, which could be rescued by fludrocortisone. An immunohistochemical study revealed renin accumulation in the juxtaglomerular cells of Rrbp1-KO mice. In the RRBP1-knockdown Calu-6 cells, a human renin-producing cell line, transmission electron and confocal microscopy revealed that renin was primarily retained in the endoplasmic reticulum and was unable to efficiently target the Golgi apparatus for secretion. CONCLUSIONS: RRBP1 deficiency in mice caused hyporeninemic hypoaldosteronism, resulting in lower blood pressure, severe hyperkalemia, and sudden cardiac death. In juxtaglomerular cells, deficiency of RRBP1 reduced renin intracellular trafficking from ER to Golgi apparatus. RRBP1 is a brand-new regulator of blood pressure and potassium homeostasis discovered in this study.

A genome-wide association study for melatonin secretion.

Melatonin exerts a wide range of effects among various tissues and organs. However, there is currently no study to investigate the genetic determinants of melatonin secretion. Here, we conducted a genome-wide association study (GWAS) for melatonin secretion using morning urine 6-hydroxymelatonin sulfate-to-creatinine ratio (UMCR). We initially enrolled 5000 participants from Taiwan Biobank in this study. After excluding individuals that did not have their urine collected in the morning, those who had history of neurological or psychiatric disorder, and those who failed to pass quality control, association of single nucleotide polymorphisms with log-transformed UMCR adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for estimated glomerular filtration rate (eGFR). A total of 2373 participants underwent the genome-wide analysis. Five candidate loci associated with log UMCR (P value ranging from 6.83 × 10-7 to 3.44 × 10-6) encompassing ZFHX3, GALNT15, GALNT13, LDLRAD3 and intergenic between SEPP1 and FLJ32255 were identified. Similar results were yielded with further adjustment for eGFR. Interestingly, the identified genes are associated with circadian behavior, neuronal differentiation, motor disorders, anxiety, and neurodegenerative diseases. We conducted the first GWAS for melatonin secretion and identified five candidate genetic loci associated with melatonin level. Replication and functional studies are needed in the future.

Accuracy of Liver-Type Fatty Acid-Binding Protein in Predicting Acute Kidney Injury: A Meta-Analysis.

BACKGROUND: Liver-type fatty acid-binding protein (L-FABP) is a promising biomarker for the early prediction of acute kidney injury (AKI). However, the clinical utility of L-FABP in different populations or settings remains unclear. We present a meta-analysis of studies evaluating the performance of L-FABP in AKI prediction. METHODS: We performed a literature search in MEDLINE, EMBASE, and Cochrane library, using search terms "acute kidney injury" and "L-FABP." Studies investigating the performance characteristics of L-FABP for the early diagnosis of AKI were included. Data about patient characteristics, diagnostic criteria of AKI, quantitative data required for construction of a 2 × 2 table (number of participants, sensitivity, specificity, and case number), study settings, and outcomes were extracted. The bivariable model was applied to calculate the estimated sensitivity and specificity of L-FABP. A summary ROC curve was created by plotting the true-positive rate against the false-positive rate at various cutoff values from different studies. RESULTS: We found 27 studies reporting measurement of urine (n = 25 studies) or plasma (n = 2 studies) L-FABP. Overall, the estimated sensitivity was 0.74 (95% CI: 0.69-0.80) and specificity was 0.78 (95% CI: 0.71-0.83). L-FABP demonstrated a stable area under the ROC of 0.82 (95% CI: 0.79-0.85) in variable clinical settings including intensive care unit, surgery, and contrast-induced AKI. In subgroup analysis excluding pediatric and post radiocontrast exposure cohorts, L-FABP had comparative diagnostic performance with neutrophil gelatinase associated lipocalin (NGAL). CONCLUSIONS: Despite broad prevalence, L-FABP is a clinically useful marker with moderate accuracy in variable clinical settings as demonstrated in our subgroup analysis. Except for pediatric patients and those post-radiocontrast exposure, L-FABP has comparable discriminative capability as NGAL.

Renin-angiotensin-aldosterone system inhibition decreased contrast-associated acute kidney injury in chronic kidney disease patients.

BACKGROUND/PURPOSE: Chronic kidney disease (CKD) is a risk factor for contrast associated acute kidney injury (CA-AKI). The risk of renin-angiotensin-aldosterone system inhibitor (RASi) use in patients with CKD before the administration of contrast is not clear. METHODS: In this nested case-control study, 8668 patients received contrast computed tomography (CT) from 2013 to 2018 during index administration in a multicenter hospital cohort. The identification of AKI is based on the Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria within 48 h after contrast medium used. RESULTS: Finally, 986 patients (age, 63.36 ± 12.22; men, 72.92%) with CKD (estimated glomerular filtration rate (eGFR) = 35.0 ± 19.8 mL/min/1.73 m2) were eligible for analysis. After the index date, RASi users (n = 315) were less likely to develop CA-AKI (13.65% vs 30.4%, p < 0.001), and had a lower hospital mortality (8.25% vs 19.23%, p < 0.001) compared with non-users. The pre-contrast use of RASi decrease the risk of AKI (OR, 0.342, p < 0.001) and hospital mortality (OR, 0.602, p = 0.045). Even a few defined daily doses (DDDs) of RASi treatment, more than 0.02 prior to contrast CT could attenuate CA-AKI. The hospital mortality was higher in RASi non-users if their eGFR value was more than 17.9 mL/min/1.73 m2. CONCLUSION: RASi use in patients with CKD prior to contrast CT has the potential to mitigate the incidence of AKI and hospital mortality. Even a low dose of RASi will noticeably decrease the risk of AKI and will not increase the risk of hyperkalemia.

Mobile Health App With Social Media to Support Self-Management for Patients With Chronic Kidney Disease: Prospective Randomized Controlled Study.

BACKGROUND: Chronic kidney disease (CKD) is a global health burden. Self-management plays a key role in improving modifiable risk factors. OBJECTIVE: The aim of this study was to evaluate the effectiveness of wearable devices, a health management platform, and social media at improving the self-management of CKD, with the goal of establishing a new self-management intervention model. METHODS: In a 90-day prospective experimental study, a total of 60 people with CKD at stages 1-4 were enrolled in the intervention group (n=30) and control group (n=30). All participants were provided with wearable devices that collected exercise-related data. All participants maintained dietary diaries using a smartphone app. All dietary and exercise information was then uploaded to a health management platform. Suggestions about diet and exercise were provided to the intervention group only, and a social media group was created to inspire the participants in the intervention group. Participants' self-efficacy and self-management questionnaire scores, Kidney Disease Quality of Life scores, body composition, and laboratory examinations before and after the intervention were compared between the intervention and control groups. RESULTS: A total of 49 participants completed the study (25 in the intervention group and 24 in the control group); 74% of the participants were men and the mean age was 51.22 years. There were no differences in measured baseline characteristics between the groups except for educational background. After the intervention, the intervention group showed significantly higher scores for self-efficacy (mean 171.28, SD 22.92 vs mean 142.21, SD 26.36; P<.001) and self-management (mean 54.16, SD 6.71 vs mean 47.58, SD 6.42; P=.001). Kidney Disease Quality of Life scores were also higher in the intervention group (mean 293.16, SD 34.21 vs mean 276.37, SD 32.21; P=.02). The number of steps per day increased in the intervention group (9768.56 in week 1 and 11,389.12 in week 12). The estimated glomerular filtration rate (eGFR) of the intervention group was higher than that of the control group (mean 72.47, SD 24.28 vs mean 59.69, SD 22.25 mL/min/1.73m2; P=.03) and the decline in eGFR was significantly slower in the intervention group (-0.56 vs -4.58 mL/min/1.73m2). There were no differences in body composition between groups postintervention. CONCLUSIONS: The use of wearable devices, a health management platform, and social media support not only strengthened self-efficacy and self-management but also improved quality of life and a slower eGFR decline in people with CKD at stages 1-4. These results outline a new self-management model to promote healthy lifestyle behaviors for patients with CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04617431; https://www.clinicaltrials.gov/ct2/show/NCT04617431.

Lactate Dehydrogenase-to-Lymphocyte Ratio Represents a Powerful Prognostic Tool of Metastatic Renal Cell Carcinoma Patients Treated with Tyrosine Kinase Inhibitors.

Inflammation parameters were verified to predict clinical outcomes of metastatic renal cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors (TKIs). Here, we developed a novel marker, lactate dehydrogenase (tumor burden marker) to lymphocytes (inflammation marker) ratio (LLR), aimed to reveal the prognostic role of LLR for mRCC patients treated with TKIs. We collected clinical data of mRCC patients treated with TKIs. Receiver operating curve analysis was used to determine the optimal cut-off value. The c-index method was used to determine the best predictive marker for overall survival (OS). Clinicopathological characteristics on OS and progression-free survival (PFS) were evaluated by univariate analysis, and multivariate analyses. LLR provided the greatest improvement in the c-index, and displayed the best marker of the prognostic accuracy for OS. Univariate analysis revealed that LLR, ECOG PS and IMDC risks were significant predictors of OS and PFS. However, multivariate analysis indicated that IMDC risks failed to predict PFS, and only showed predictor of OS. We finally stratifed patients into low LLR (<150) and high LLR (≥150) group with different clinical outcomes. LLR represents a powerful prognostic tool of clinical outcome in mRCC patients treated with TKIs.

A immunosuppressive triterpenoid saponin from the stems of Epigynum griffithianum.

Chemical investigation of the stems of Epigunum griffithianum led to the isolation and identification of a new triterpenoid saponin (1) and two known compounds (epigynosides A (2) and B (3)). These structures were elucidated by means of spectroscopic analysis (1D and 2D NMR, MS, UV, IR) as well as comparison with the reported data. Compound 1 was evaluated in vitro for the immunosuppressive activities on proliferation of mice splenocyte and displayed significant immunosuppressive activities compared to the positive control (dexamethasone) with the concentration at 25 µM.[Formula: see text].

Pioglitazone improves hepatic mitochondrial function in a mouse model of nonalcoholic steatohepatitis.

Pioglitazone is effective in improving insulin resistance and liver histology in patients with nonalcoholic steatohepatitis (NASH). Because dysfunctional mitochondrial metabolism is a central feature of NASH, we hypothesized that an important target of pioglitazone would be alleviating mitochondrial oxidative dysfunction. To this end, we studied hepatic mitochondrial metabolism in mice fed high-fructose high-transfat diet (TFD) supplemented with pioglitazone for 20 wk, using nuclear magnetic resonance-based 13C isotopomer analysis. Pioglitazone improved whole body and adipose insulin sensitivity in TFD-fed mice. Furthermore, pioglitazone reduced intrahepatic triglyceride content and fed plasma ketones and hepatic TCA cycle flux, anaplerosis, and pyruvate cycling in mice with NASH. This was associated with a marked reduction in most intrahepatic diacylglycerol classes and, to a lesser extent, some ceramide species (C22:1, C23:0). Considering the cross-talk between mitochondrial function and branched-chain amino acid (BCAA) metabolism, pioglitazone's impact on plasma BCAA profile was determined in a cohort of human subjects. Pioglitazone improved the plasma BCAA concentration profile in patients with NASH. This appeared to be related to an improvement in BCAA degradation in multiple tissues. These results provide evidence that pioglitazone-induced changes in NASH are related to improvements in hepatic mitochondrial oxidative dysfunction and changes in whole body BCAA metabolism.

Genome Wide Association Study Identifies the HMGCS2 Locus to be Associated With Chlorthalidone Induced Glucose Increase in Hypertensive Patients.

BACKGROUND: Thiazide and thiazide-like diuretics are first-line medications for treating uncomplicated hypertension. However, their use has been associated with adverse metabolic events, including hyperglycemia and incident diabetes mellitus, with incompletely understood mechanisms. Our goal was to identify genomic variants associated with thiazide-like diuretic/chlorthalidone-induced glucose change. METHODS AND RESULTS: Genome-wide analysis of glucose change after treatment with chlorthalidone was performed by race among the white (n=175) and black (n=135) participants from the PEAR-2 (Pharmacogenomic Evaluation of Antihypertensive Responses-2). Single-nucleotide polymorphisms with P<5×10-8 were further prioritized using in silico analysis based on their expression quantitative trait loci function. Among blacks, an intronic single-nucleotide polymorphism (rs9943291) in the HMGCS2 was associated with increase in glucose levels following chlorthalidone treatment (ß=12.5; P=4.17×10-8). G-allele carriers of HMGCS2 had higher glucose levels (glucose change=+16.29 mg/dL) post chlorthalidone treatment compared with noncarriers of G allele (glucose change=+2.80 mg/dL). This association was successfully replicated in an independent replication cohort of hydrochlorothiazide-treated participants from the PEAR study (ß=5.54; P=0.023). A meta-analysis of the 2 studies was performed by race in Meta-Analysis Helper, where this single-nucleotide polymorphism, rs9943291, was genome-wide significant with a meta-analysis P value of 3.71×10-8. HMGCS2, a part of the HMG-CoA synthase family, is important for ketogenesis and cholesterol synthesis pathways that are essential in glucose homeostasis. CONCLUSIONS: These results suggest that HMGCS2 is a promising candidate gene involved in chlorthalidone and Hydrochlorothiazide (HCTZ)-induced glucose change. This may provide insights into the mechanisms involved in thiazide-induced hyperglycemia that may ultimately facilitate personalized approaches to antihypertensive selection for hypertension treatment. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00246519 and NCT01203852.

Relative Bioavailability of Silybin A and Silybin B From 2 Multiconstituent Dietary Supplement Formulations Containing Milk Thistle Extract: A Single-dose Study.

PURPOSE: The purpose of this study was to compare the bioavailability between 2 milk thistle-containing dietary supplements, Product B and IsaGenesis, in healthy volunteers. METHODS: Bioavailability between Product B, originally formulated as a powdered capsule, and IsaGenesis, reformulated as a soft gel, were compared by measuring silybin A and silybin B as surrogate pharmacokinetic markers for differences in absorption and bioavailability. For this randomized, open-label, crossover pharmacokinetic study, 12 healthy volunteers consumed a single-dose serving of each supplement separated by at least a 7-day washout period. Serial blood samples were obtained at 0, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and analyzed via LC-MS/MS. FINDINGS: Rapid absorption and elimination of silybin A and silybin B have been observed after oral administration of both Product B and IsaGenesis. However, the absorption rate and extent, as indicated by mean the Cmax and mean plasma AUC, were significantly higher for the IsaGenesis soft gel formulation. The dose-corrected mean Cmax was 365% and 450% greater for silybin A and B, respectively, relative to powdered Product B. The time to Tmax was reached, on average, at least 1 hour earlier with IsaGenesis relative to Product B for both silybin A and silybin B. IMPLICATIONS: The IsaGenesis soft gel formulation provided substantially greater absorption and bioavailability of silybin A and silybin B relative to the powdered Product B supplement. ClinicalTrials.gov Identifier: NCT02529605.

Comparison of outcomes between emergent-start and planned-start peritoneal dialysis in incident ESRD patients: a prospective observational study.

BACKGROUND: The clinical consequences of starting chronic peritoneal dialysis (PD) after emergent dialysis via a temporary hemodialysis (HD) catheter has rarely been evaluated within a full spectrum of treated end-stage renal disease (ESRD). We investigated the longer-term outcomes of patients undergoing emergent-start PD in comparison with that of other practices of PD or HD in a prospective cohort of new-onset ESRD. METHODS: This was a 2-year prospective observational study. We enrolled 507 incident ESRD patients, among them 111 chose PD (43 planned-start, 68 emergent-start) and 396 chose HD (116 planned-start, 280 emergent-start) as the long-term dialysis modality. The logistic regression model was used to identify variables associated with emergent-start dialysis. The Kaplan-Meier survival analysis was used to determine patient survival and technique failure. The propensity score-adjusted Cox regression model was used to identify factors associated with patient outcomes. RESULTS: During the 2-year follow-up, we observed 5 (4.5%) deaths, 15 (13.5%) death-censored technique failures (transfer to HD) and 3 (2.7%) renal transplantations occurring in the PD population. Lack of predialysis education, lower predialysis estimated glomerular filtration rate and serum albumin were predictors of being assigned to emergent dialysis initiation. The emergent starters of PD displayed similar risks of patient survival, technique failure and overall hospitalization, compared with the planned-start counterparts. By contrast, the concurrent planned-start and emergent-start HD patients with an arteriovenous fistula or graft were protected from early overall death and access infection-related mortality, compared with the emergent HD starters using a central venous catheter. CONCLUSIONS: In late-referred chronic kidney disease patients who have initiated emergent dialysis via a temporary HD catheter, post-initiation PD can be a safe and effective long-term treatment option. Nevertheless, due to the potential complications and cost concerns, such practice of PD initiation would better be replaced with a planned-start mode by employing more effective predialysis therapeutic education and timely catheter placement.

Anti-Yo positive and late-onset paraneoplastic cerebellar degeneration associated with ovarian carcinoma: A case report.

RATIONALE: Paraneoplastic cerebellar degeneration (PCD) is a rare nonmetastatic neurological complication often associated with ovarian, breast, and other gynecologic cancers. Anti-Yo is one of the antionconeural antibodies found in patients with PCD. It primarily emerges before a malignancy is detected. PATIENT CONCERNS: In this report, we describe an unusual case involving a patient who exhibited anti-Yo-positive PCD 1 year after being diagnosed with ovarian cancer. DIAGNOSES: Histopathology of the resected tissues and Antineuronal antibody testing. INTERVENTIONS: The patient was treated with intravenous immunoglobulin (IVIG, 1 g/d) for 1 week and a large-dose of methylprednisolone (0.4 g/kg/d) for 5 days. At the same time, underlying complications were prevented actively, and the peripheral nerves were protected. OUTCOMES: Although most patients with anti-Yo-positive PCD do not improve after treatment, our patient significantly improved after receiving active and effective treatment.

[Chemical Constituents from the Roots of Lindera glauca and Their Antitumor Activity on Four Different Cancer Cell Lines].

Objective: To study the chemical constitutes from the roots of Lindera glauca and the alkaloids influence on proliferation of HT-29,SGC-7901,SMMC-7721 and A549 cell lines. Methods: The constituents were isolated by column chromatography such as RP-18,Sephadex LH-20 and silica gel,and their structures were elucidated by spectroscopic data analysis and compared with literature data. The antitumor activity was determined by MTT assay. Results: Ten compounds had been isolated and identified as(-)-magnocurarine( 1),N-methyl-laurotetanine( 2),laurotetanine( 3),( +)-boldine( 4),(-)-norisoboldine( 5),( +)-norisocorydine( 6),pmethane-3,8-trans-diol( 7),p-methane-3,8-cis-diol( 8),eudesm-4( 15)-ene-7,11-diol( 9) and 4ß,6ß-dihydroxy-1α,5ß( H)-guai-9-ene( 10). Compounds 2 ~ 4 showed significant inhibitory activities against HT-29,SGC-7901,SMMC-7721 and A549 cells. Conclusion: Compound 1,9 and 10 are isolated from this plant for the first time. The IC50 value of compound 2 against HT-29 and SGC-7901 cell lines is even lower than VP-16.

Crystal Structure and Antibacterial Activity of (E)-(5-ethyl-2-styryl-1,3-dioxan-5-yl) Methanol Synthesized with Nanosolid Superacid.

A new chiral 1,3-dioxane compound was synthesized by aldol condensation reaction in this paper. The reaction of cinnamic aldehyde with 2.1 equiv. of 2,2-bis(hydroxymethyl) butanol in N,N-dimethylformamide and cyclohexane, nanosolid superacid SO4(2-)/Fe2O3 was applied as catalyst, afforded the new chiral 1,3-dioxane compound (E)-(5-ethyl-2-styryl-1,3-dioxan-5-yl) methanol. The compound was fully characterized with infrared spectra, elemental analysis, melting points, 1H NMR and X-ray diffraction. Single crystal X-ray diffraction analysis revealed that the compound crystallized in the monoclinic system, space group P2(1) with a = 5.717(2) Å, b = 11.684(4) Å, c = 10.569(4) Å, α = 90.00 degrees, ß = 99.646(4) degrees, γ = 90.00 degrees, V = 696.0(4) Å3, Z = 2, Dc = 1.185 g/cm(-3), R = 0.0182, µ = 0.081 mm(-1), F(000) = 268. In addition, the antibacterial activities of the compound against Bacillus subtilis, Escherichia coli and Staphylococcus aureus have been investigated.

Impact of weaning from acute dialytic therapy on outcomes of chronic kidney disease following urgent-start dialysis.

Discontinuation of acute, unplanned dialysis is always an important therapeutic goal in dialysis-requiring patients with existing chronic kidney disease. Only a limited proportion of patients could be weaned off dialysis and remained dialysis-free. Here we performed a multicenter, observational study to investigate factors associated with successful weaning from acute dialysis, and to explore the potential impact of weaning itself on outcomes of patients with chronic kidney disease following urgent-start dialysis. We recruited 440 chronic kidney disease patients with a baseline estimated glomerular filtration rate <45 ml/min per 1/73 m2, and used propensity score-adjusted Cox regression analysis to measure the effect of weaning from acute dialysis on death during the index hospitalization and death or readmission after discharge. Over 2 years, 64 of 421 (15.2%) patients who survived >1 month died, and 36 (8.6%) were removed from dialysis, with 26 (6.2%) remaining alive and dialysis-free. Logistic regression analysis found that age ≧ 65 years, ischemic acute tubular necrosis, nephrotoxic exposure, urinary obstruction, and higher predialysis estimated glomerular filtration rate and serum hemoglobin were predictors of weaning off dialysis. After adjustment for propensity scores for dialysis weaning, Cox proportional hazards models showed successful weaning from dialysis (adjusted hazard ratio 0.06; 95% confidence interval 0.01 to 0.35), along with a history of hypertension and serum albumin, were independent protectors for early death. Conversely, a history of stroke, peripheral arterial disease and cancer predicted the occurrence of early mortality. In conclusion, this prospective cohort study shows that compared to patients with chronic kidney disease who became end-stage renal disease after acute dialysis, patients who could be weaned off acute dialytic therapy were associated with reduced risk of premature death over a 2-year observation period.