Association of albumin to non-high-density lipoprotein cholesterol ratio with mortality in peritoneal dialysis patients.

OBJECTIVE: Malnutrition and inflammation are associated with mortality in peritoneal dialysis (PD) patients. Serum albumin and non-high-density lipoprotein cholesterol (non-HDL-C) are independently associated with mortality in PD patients. Combining albumin and non-HDL-C with mortality may be more plausible in clinical practice. METHODS: This retrospective cohort study included 1954 Chinese PD patients from 1 January 2009 to 31 December 2016. Kaplan-Meier curve was used to determine the relationship between albumin to non-HDL-C ratio and all-cause mortality. Cox regression analysis was applied to assess the independent predictive value while adjusting for confounding factors. Competitive risk analysis was used to examine the effects of other outcomes on all-cause mortality prognosis. RESULTS: In the 33-month follow-up period, there were 538 all-cause deaths. Kaplan-Meier analysis presented significant differences in all-cause mortality. Multivariate Cox regression showed that the risk of all-cause mortality was lower in the moderate group (9.36-12.79) (HR, 0.731; 95% CI, 0.593-0.902, p = 0.004) and the highest group (>12.79) (HR, 0.705; 95% CI, 0.565-0.879, p = 0.002) compared to the lowest group (≤9.36). Competitive risk analysis revealed significant differences for all-cause mortality (p < 0.001), while there was no statistical significance for other competing events. CONCLUSIONS: Low albumin to non-HDL-C ratio was associated with a high risk of all-cause mortality in PD patients. It may serve as a potential prognostic biomarker in PD patients.

High Bile Titer and High Bile to Serum Ratio of CYFRA 21 - 1 Reliably Discriminate Malignant Biliary Obstruction Caused by Cholangiocarcinoma.

INTRODUCTION: Previously we demonstrated that elevated serum CYFRA 21 - 1 is a reliable diagnostic and prognostic biomarker for biliary tract cancers. This study aims to explore the diagnostic performance of bile CYFRA 21 - 1 (bCYFRA 21 - 1) in discriminating malignant biliary obstruction (MBO) caused by cholangiocarcinoma (CCA). METHODS: 77 CCA patients ((17 intrahepatic CCA (iCCA), 49 perihilar CCA (pCCA) and 11 distal CCA (dCCA)) and 43 benign patients with biliary obstruction were enrolled. Serum and bile levels of CYFRA 21 - 1, carcinoembryonic antigen (CEA) and carbohydrate antigen 19 - 9 (CA19-9) were quantified. Diagnostic performances of these biomarkers were estimated by receiver operator characteristic curves. Subgroups analysis of these tumor markers among CCA subtypes was performed. RESULTS: High bCYFRA 21 - 1 (cut-off value of 59.25 ng/mL with sensitivity of 0.889 and specificity of 0.750) and high bile to serum ratio of CYFRA 21 - 1 (b/sCYFRA 21 - 1, cut-off value of 31.55 with sensitivity of 0.741 and specificity of 0.778) achieved better diagnostic performance than any other biomarker in discriminating MBO. Subgroup analysis revealed that bCYFRA 21 - 1 was significantly elevated in all CCA subtypes; moreover b/sCYFRA 21 - 1 was upregulated in pCCA and dCCA (the mean b/sCYFRA 21 - 1 of pCCA was highest among CCA subtypes: 57.90, IQR 29.82-112.27). CONCLUSIONS: Both high biliary CYFRA 21 - 1 and high bile to serum ratio of CYFRA 21 - 1 were reliable diagnostic biomarkers for MBO caused by CCA.

High Thermal Stability and Low Thermal Resistance of Large Area GaN/3C-SiC/Diamond Junctions for Practical Device Processes.

Thermal management is critical in contemporary electronic systems, and integrating diamond with semiconductors offers the most promising solution to improve heat dissipation. However, developing a technique that can fully exploit the high thermal conductivity of diamond, withstand high-temperature annealing processes, and enable mass production is a significant challenge. In this study, the successful transfer of AlGaN/GaN/3C-SiC layers grown on Si to a large-size diamond substrate is demonstrated, followed by the fabrication of GaN high electron mobility transistors (HEMTs) on the diamond. Notably, no exfoliation of 3C-SiC/diamond bonding interfaces is observed even after annealing at 1100 °C, which is essential for high-quality GaN crystal growth on the diamond. The thermal boundary conductance of the 3C-SiC-diamond interface reaches ≈55 MW m-2 K-1, which is efficient for device cooling. GaN HEMTs fabricated on the diamond substrate exhibit the highest maximum drain current and the lowest surface temperature compared to those on Si and SiC substrates. Furthermore, the device thermal resistance of GaN HEMTs on the diamond substrate is significantly reduced compared to those on SiC substrates. These results indicate that the GaN/3C-SiC on diamond technique has the potential to revolutionize the development of power and radio-frequency electronics with improved thermal management capabilities.

Association of Neutrophil and Albumin With Mortality Risk in Patients Receiving Peritoneal Dialysis.

OBJECTIVE: Inflammation and nutrition have been recognized as predicting mortality in patients receiving peritoneal dialysis (PD). Serum neutrophil and albumin are crucial factors in inflammation and nutrition status. Up until now, the synergistic effect of neutrophil and albumin on mortality prediction in PD patients is still being determined. Our study sought to assess the effect of the interaction between neutrophils and albumin on the risk of all-cause mortality and cardiovascular disease (CVD) mortality patients receiving PD. METHODS: A total of 1229 PD patients were recruited and divided into three categories in this cohort study. Their relationships with all-cause mortality and CVD mortality were analyzed in multivariable COX regression models adjusted for confounding factors. RESULTS: During the median follow-up of 34.2 months, 222 (18.1%) patients died, and 115 (51.8%) suffered from cardiovascular events. Patients with high neutrophil percentage-to-albumin ratio (NPAR) showed increased all-cause mortality and CVD mortality, with adjusted hazard ratios of 1.490 (95% confidence interval, 1.070-2.074, P = .018) and 1.633 (95% confidence interval, 1.041-2.561, P = .033), respectively, compared with those with low NPAR. Competitive risk models and sensitivity analyses further confirmed this association. In the receiver operating characteristic curve analysis, however, there was little evidence that NPAR is a better indicator than albumin and neutrophil count. CONCLUSIONS: Having a high NPAR is linked to a higher risk of mortality, especially when both high neutrophil and low albumin are present.

Synthesis of ethane-disulfonate pillared layered cobalt hydroxide towards the electrocatalytic oxygen evolution reaction.

We report the synthesis of a hybrid layered cobalt hydroxide sample and its redox behaviors in the electrochemical oxygen evolution reaction (OER). Compound Co7(OH)12(C2H4S2O6)·1.6H2O was synthesized via a homogeneous alkalization reaction using Co(SO3C2H4SO3) and hexamethylenetetramine. This compound comprises cationic host layers of {[Co7(OH)12]2+}∞, which comprise octahedrally (CoOh) and tetrahedrally (CoTd) coordinated Co cations at a CoOh : CoTd ratio of 5 : 2. The ethane-disulfonate ions are combined with the cationic host layers by electrostatic attractions and hydrogen bonding as a hybrid pillared layered framework. This hybrid sample can promote the OER in 1 M KOH with an overpotential as low as ∼410 mV (at a current density of 10 mA cm-2). In situ Raman spectroscopy showed that the sample first evolved into Co(III)-based phases comprising a mixture of layered CoOOH and spinel Co3O4, and the Co(III)-based compounds were converted into Co(IV)-O intermediates containing [CoO6] units at the onsite of the OER. The structural evolution behaviors suggest that the catalyst prefers a topotactic phase transition and the CoOh and CoTd units exhibit different activities in the electrochemical reaction. The electron transfer events involved in the electrochemical reaction were identified by Fourier-transformed alternating current voltammetry.

Gonadal Y-chromosome mosaicism with 45, X Turner syndrome complicated with bilateral HCG-secreting gonadoblastoma.

We report a rare case of bilateral HCG-secreting gonadoblastomas (Gb) in a 5.25-year-old girl of 45, X Turner syndrome (TS) with gonadal Y chromosome mosaicism. The clinical data were summarized, and the literatures were reviewed. The patient had enlarged breasts for 2 years and 3 months, with elevated ß-HCG of blood found for 8 months. The level of ß-HCG of cerebrospinal fluid, cranial MRI, chest and abdominal CT, and pelvic MRI were normal. After surgical gonad exploration, biopsy and excision, gonad venous blood hormone examination and SRY gene detection of gonad tissue, the diagnosis was confirmed as HCG-secreting Gb (bilateral) and TS (45, X) with gonad Y chromosome mosaicism. The patient received 4 courses of chemotherapy, and regular outpatient follow-up. At 9 months after gonadectomy, there was no clinical, laboratory, or radiological evidence of recurrence. We reported a nonclassical case of 45, X Turner syndrome (TS) with gonadal Y chromosome mosaicism, who presented with breast development as the first manifestation and then virilization due to bilateral HCG-secreting gonadoblastomas. Detection of serum ß-HCG and AFP is requisite for the diagnosis of precocious puberty, karyotyping is important for virilizing phenotypic female, and virilization in Turner syndrome implies the existence of Y chromosome(substance) (peripheral blood or tissue mosaicism) and the occurrence of gonadal tumors.

High thermal conductivity in wafer-scale cubic silicon carbide crystals.

High thermal conductivity electronic materials are critical components for high-performance electronic and photonic devices as both active functional materials and thermal management materials. We report an isotropic high thermal conductivity exceeding 500 W m-1K-1 at room temperature in high-quality wafer-scale cubic silicon carbide (3C-SiC) crystals, which is the second highest among large crystals (only surpassed by diamond). Furthermore, the corresponding 3C-SiC thin films are found to have record-high in-plane and cross-plane thermal conductivity, even higher than diamond thin films with equivalent thicknesses. Our results resolve a long-standing puzzle that the literature values of thermal conductivity for 3C-SiC are lower than the structurally more complex 6H-SiC. We show that the observed high thermal conductivity in this work arises from the high purity and high crystal quality of 3C-SiC crystals which avoids the exceptionally strong defect-phonon scatterings. Moreover, 3C-SiC is a SiC polytype which can be epitaxially grown on Si. We show that the measured 3C-SiC-Si thermal boundary conductance is among the highest for semiconductor interfaces. These findings provide insights for fundamental phonon transport mechanisms, and suggest that 3C-SiC is an excellent wide-bandgap semiconductor for applications of next-generation power electronics as both active components and substrates.

Proton pump inhibitor usage associates with higher risk of first episodes of pneumonia and peritonitis in peritoneal dialysis patients.

BACKGROUND: A large number of studies have shown that proton pump inhibitors (PPIs) are associated with infection events. Therefore, we retrospectively evaluated the association of PPI therapy with the occurrence of first pneumonia and peritoneal dialysis(PD)-related peritonitis events in the maintenance PD patients. METHODS: We collected PD patients in two large hospitals from January 1, 2012 to December 31, 2016, and divided them into the PPI group and the non-PPI group. Multivariate Cox proportional hazards models were applied to evaluate the cumulative incidence and hazard ratios (HRs). Inverse probability of treatment weight (IPTW) method was used to adjust for covariate imbalance between the two groups and further confirm our findings. RESULTS: Finally, 656 PD patients were included for data analysis, and the results showed that PPI usage was associated with an increased risk of pneumonia [HR 1.71; 95% CI 1.06-2.76; p = 0.027] and peritonitis [HR 1.73; 95% CI 1.24-2.40; p = 0.001]. IPTW-adjusted HRs for the association of PPIs with pneumonia and peritonitis were 1.58 (95% CI:1.18-2.12; p = 0.002) and 2.33 (95% CI:1.91-2.85; p < 0.001), respectively. Moreover, the competitive risk model proved that under the conditions of competition for other events(including transfer to hemodialysis therapy, kidney transplant, transfer from our research center, loss to follow-up, and death), the differences in endpoints events between the two groups were still statistically significant (p = 0.009, p < 0.001, respectively). CONCLUSIONS: PPIs was associated with an increased risk of first pneumonia and PD-related peritonitis events in PD patients, which reminds clinicians to be cautious when prescribing acid-suppressing drugs for PD patients.

Parthenolide alleviates peritoneal fibrosis by inhibiting inflammation via the NF-κB/ TGF-ß/Smad signaling axis.

Peritoneal fibrosis is a common complication of peritoneal dialysis (PD) with a complicated pathogenesis and limited treatments. Parthenolide (PTL), a recognized nuclear factor-κB (NF-κB) inhibitor extracted from Tanacetum balsamita, has been widely used to treat various inflammatory diseases and has been proven to improve peritoneal fibrosis in PD mice by selectively inhibiting the phosphorylation of Smad2/3. Transforming growth factor-ß1 (TGF-ß1), via Smad-dependent signaling, has a pivotal role in promoting pathogenic of fibrosis. To investigate whether PTL can inhibit peritoneal fibrosis, we affected the interaction between NF-κB and the TGF-ß/Smad2/3 pathway. Long dwell peritoneal dialysis fluid (PDF) and peritoneum tissues were collected from continuous ambulatory peritoneal dialysis (CAPD) patients. PTL was administered intragastrically into a PD mouse model by daily infusion of 4.25% dextrose-containing PDF. Treated HMrSV5 cells or rat peritoneal mesothelial cells (RPMCs) were treated with high glucose(138 mM) at the same concentration as 2.5% dextrose-containing PDF and PTL. PD-related peritoneal fibrosis samples indicated an increase in inflammation, and PTL decreased the levels of inflammatory cytokines (L-6, TNF-α, and MCP-1). PTL inhibited high glucose-induced mesothelial-to-mesenchymal transition (MMT), as indicated by a reduced expression of fibrosis markers (fibronectin, collagen I, and α-SMA) and increased expression of the epithelial marker E-cadherin. PTL also significantly decreased TGF-ß1 expression and the phosphorylation of IκBα and NF-κBp65. The changes in the levels of TGF-ß1 expression and p-p65 or p65 showed similar trends according to western blot, immunohistochemistry, and immunofluorescence assays in vitro and in vivo. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were used to confirm that PTL regulates the transcription of TGF-ß1 induced by high glucose through NF-κBp65. In summary, PTL induces a therapeutic effect in peritoneal fibrosis by inhibiting inflammation via the NF-κB/ TGF-ß/Smad signaling axis.

[Corrigendum] Screening of hub genes and evaluation of the growth regulatory role of CD44 in metastatic prostate cancer.

Subsequently to the publication of the above article, the authors have realized that they inadvertently included images of the same mice in Figs. 7A [the Negative Control (NC) experiment] and 8A [the 5B­3CT + Docetaxel (10 mg/kg) experiment]. After having consulted their original data, the authors have realized that these mice were correctly shown in the paper for the experiments portrayed in Fig. 7A; therefore, the corrected version of Fig. 8 is shown on the next page, showing the mice pertaining to the 5B­3CT + Docetaxel (10 mg/kg) experiment in Fig. 8A. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish a Corrigendum, and all the authors agree to this Corrigendum. Furthermore, they apologize to the readership for any inconvenience caused. [Oncology Reports 46: 196, 2021; DOI: 10.3892/or.2021.8147].

Neutrophil to high-density lipoprotein ratio associates with higher all-cause mortality and new onset cardiovascular events in peritoneal dialysis patients.

BACKGROUND: Neutrophil to high-density lipoprotein ratio (NHR), a new inflammatory marker, is associated with poor clinical prognosis. However, the correlation of NHR and adverse outcomes in peritoneal dialysis (PD) patients remains unclear. METHODS: In this retrospective cohort study, a total of 1051 PD patients were recruited from three centers during Jan 1, 2009 to Dec 31, 2017. Eligible patients were distributed according to quartiles of the NHR. Kaplan-Meier cumulative incidence curves, multivariate COX regression, competitive risk analysis and restricted cubic spline (RCS) were applied to analyze the relationship between NHR and all-cause mortality as well as cardiovascular events (CVE). In addition, forest plots were used to calculate the interaction between different subgroups. RESULTS: During follow-up, a total of 240 all-cause mortality and 157 new-onset CVE were recorded. The all-cause mortality in the highest quartile of NHR (> 5.43) were higher than those in the other groups. RCS showed a non-linear relationship between NHR and adverse outcomes. Multivariate COX regression indicated elevated NHR was an independent risk factor for all-cause mortality. Compared to the highest quartile, hazard ratio (HR) of new-onset CVE equals to 0.522 (95% CI 0.321-0.849) in the secondary quartile (2.43 < NHR ≤ 3.57), and the HR of all-cause mortality analysis is 0.551 (95% CI 0.378-0.803) in the third quartile (3.57 < NHR ≤ 5.43). Kaplan-Meier analysis suggested there were significant differences in all-cause mortality and new-onset CVE among four NHR groups. CONCLUSIONS: NHR was a new independent risk factor for all-cause mortality in PD patients.

Proton pump inhibitor usage is associated with higher all-cause mortality and CV events in peritoneal dialysis patients.

OBJECTIVES: A long period of inappropriate proton pump inhibitors (PPI) treatment has been proved to be associated with adverse prognosis in general population and hemodialysis patients. This study was conducted to clarify the impact of PPI usage on mortality and adverse cardiovascular (CV) events in peritoneal dialysis (PD) patients. METHODS AND DESIGN: This is a retrospective study. A total of 905 patients were enrolled from two PD centers, including 211 patients on PPI treatment and 618 patients not on PPIs. Kaplan-Meier curves were used to identify the incidence of adverse outcomes. Multivariate Cox regression models and inverse probability of treatment weighting (IPTW) were applied to analyze hazard ratios (HRs) for adverse outcomes. RESULTS: During follow-up, 162 deaths and 102 CV events were recorded. Kaplan-Meier curve demonstrated all-cause mortality (log-rank test p = .018) and CV events (log-rank test p = .024) were significantly higher in PPI usage group. Multivariate Cox regression models and IPTW showed that PPI usage was an indicator for all-cause mortality (HR = 1.35, 95%CI = 1.09-1.67, p = .006) and CV events (HR = 1.78, 95%CI = 1.35-2.32, p < .001). CONCLUSIONS: PPI usage is associated with higher all-cause mortality and CV events in PD patients. Clinicians are supposed to be more careful when using PPI and need to master the indications more rigorously in patients receiving PD treatment.

ACEi/ARBs associate with lower incidence of gastrointestinal bleeding in peritoneal dialysis patients.

BACKGROUND: Gastrointestinal bleeding (GIB) is widespread in patients with impaired renal function. Whether angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARBs) potentially take a crucial role in avoiding GIB incidence among peritoneal dialysis (PD) patients is unknown. METHODS: Overall, 734 PD patients were enrolled after using propensity score matching. Kaplan-Meier analysis and COX regression were used to explore correlation between ACEi/ARBs and GIB. Competitive risk model was aimed to identify whether other events were confounding factors. Forest plot was applied to assess the influence of ACEI/ARBs on GIB incidence in different groups. RESULTS: During 8-year follow-up, 89 (12.13%) cases of GIB were recorded. Kaplan-Meier analysis revealed that the incidence of GIB among patients taking ACEi/ARBs was lower than those subjects who had not (log rank = 6.442, P = 0.011). After adjusted different confounding factors, administration of ACEi/ARBs was associated with lowered GIB incidence (adjusted HR = 0.49, 95% CI 0.32-0.77, P = 0.002). In competitive risk model, considering of other events, the incidence of GIB in two groups was still statistically significant (P = 0.010). Subgroup analysis showed ACEi/ARBs taking impeded GIB in the ≥ 60 age group (HR = 0.52, 95% CI 0.28-0.98, P = 0.040). CONCLUSION: PD patients who were submitted to ACEi/ARBs inclined to have a lower risk for GIB. In this regard, ACEi/ARBs offered a promising choice to GIB.

The CYP3A5 and ABCB1 Gene Polymorphisms in Kidney Transplant Patients and Establishment of Initial Daily Tacrolimus Dosing Formula.

BACKGROUND: Tacrolimus is an immunosuppressive drug used to prevent organ rejections. Many factors could influence blood concentration of tacrolimus. OBJECTIVE: To detect genotypes of cytochrome P450 3A5 (CYP3A5) and ABCB1 in kidney transplant patients and establish initial daily tacrolimus dosing formula based on genotypes of CYP3A5 and ABCB1 and patients' clinical parameters. METHODS: Sequence specific primer polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism were used to detect genotypes of CYP3A5 and ABCB1. The blood cell, procalcitonin, C-reactive protein, height, weight, age, gender and other clinical parameters were recorded. Multiple linear regression analysis and Pearson correlation analysis were used to conduct date analysis. RESULTS: 102 cases were enrolled in cohort 1, and there were 10 cases of CYP3A5 *1/*1 (9.8%), 28 cases of CYP3A5 *1/*3 (27.5%), and 64 cases of CYP3A5 *3/*3 (62.7%). The distributions of ABCB1 C3435T genotype were CC 36 (35.3%), CT 52 (51.0%), and TT 14 (13.7%). The distributions of ABCB1 G2677T/A genotype were GG 39 (38.2%), GT 40 (39.2%), and TT 23 (22.5%). The formula was 7.499 + (0.053 × Weight) - (0.029 × Hemoglobin concentration) - (1.045 × CYP3A5 genotype) (CYP3A5 genotype: *1/*1 type inputs 0, *1/*3 type inputs 1, *3/*3 type inputs 2). The predicted doses from the established formula had a significant correlation (r = 0.605) with actual clinical doses (P < 0.05). CONCLUSION AND RELEVANCE: Hemoglobin concentration, weight, and CYP3A5 genotype should be considered using tacrolimus. The initial daily tacrolimus dosing formula established can make a good prediction.

Novel biomarker panel for the diagnosis and prognosis assessment of sepsis based on machine learning.

Background: The authors investigated a panel of novel biomarkers for diagnosis and prognosis assessment of sepsis using machine learning (ML) methods. Methods: Hematological parameters, liver function indices and inflammatory marker levels of 332 subjects were retrospectively analyzed. Results: The authors constructed sepsis diagnosis models and identified the random forest (RF) model to be the most optimal. Compared with PCT (procalcitonin) and CRP (C-reactive protein), the RF model identified sepsis patients at an earlier stage. The sepsis group had a mortality rate of 36.3%, and the RF model had greater predictive ability for the 30-day mortality risk of sepsis patients. Conclusion: The RF model facilitated the identification of sepsis patients and showed greater accuracy in predicting the 30-day mortality risk of sepsis patients.

Fabrication of GaN/Diamond Heterointerface and Interfacial Chemical Bonding State for Highly Efficient Device Design.

The direct integration of gallium nitride (GaN) and diamond holds much promise for high-power devices. However, it is a big challenge to grow GaN on diamond due to the large lattice and thermal-expansion coefficient mismatch between GaN and diamond. In this work, the fabrication of a GaN/diamond heterointerface is successfully achieved by a surface activated bonding (SAB) method at room temperature. A small compressive stress exists in the GaN/diamond heterointerface, which is significantly smaller than that of the GaN-on-diamond structure with a transition layer formed by crystal growth. A 5.3 nm-thick intermediate layer composed of amorphous carbon and diamond is formed at the as-bonded heterointerface. Ga and N atoms are distributed in the intermediate layer by diffusion during the bonding process. Both the thickness and the sp2 -bonded carbon ratio of the intermediate layer decrease as the annealing temperature increases, which indicates that the amorphous carbon is directly converted into diamond after annealing. The diamond of the intermediate layer acts as a seed crystal. After annealing at 1000 °C, the thickness of the intermediate layer is decreased to approximately 1.5 nm, where lattice fringes of the diamond (220) plane are observed.

Screening of hub genes and evaluation of the growth regulatory role of CD44 in metastatic prostate cancer.

Prostate cancer (PCa) is the most common cancer type in men worldwide. Currently, the management of metastatic PCa (mPCa) remains a challenge to urologists. The analysis of hub genes and pathways may facilitate the understanding of the molecular mechanism of PCa. In the present study, to identify the hub genes in the mPCa, the three datasets GSE3325, GSE6919 and GSE38241 were downloaded from the platform of the Gene Expression Omnibus and function enrichment analysis of differentially expressed genes (DEGs) was performed. A total of 168 DEGs were obtained and the DEGs were significantly enriched in 'cell junction' and 'cell adhesion', among others. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis demonstrated that DEGs were enriched in three pathways including 'focal adhesion', 'renal cell carcinoma' and 'Hippo signaling pathway'. The results of the protein­protein interaction network revealed that the hub genes in mPCa were separately PTEN, Rac GTPase­activating protein 1, protein regulator of cytokinesis 1, PDZ binding kinase, centromere­associated protein E, NUF2 component of NDC80 kinetochore complex, TPX2 microtubule nucleation factor, SOX2, CD44 and ubiquitin­like with PHD and ring finger domains 1. As a hub gene, CD44 was differentially expressed in PCa, as determined by Oncomine analysis. Further experiments in vivo demonstrated that SB­3CT, a selective matrix metalloproteinase inhibitor that has been reported to block CD44 cleavage and inhibit the downstream signaling pathway, suppressed the tumorigenicity of PCa cells by decreasing the expression levels of pyruvate dehydrogenase kinase 1 and 6­phosphofructo­2­kinase/fructose­2,6­biphosphatase 4. Moreover, the combination therapy with SB­3CT and docetaxel was more effective in inhibiting PCa compared with monotherapy. In conclusion, the identification of DEGs and the in vivo experimental results helped to elucidate the molecular mechanisms of PCa and provided a potential strategy for the treatment of PCa.

High Neutrophil/Lymphocyte Ratio as an Independent Risk Factor for the First Occurrence of Stroke in Peritoneal Dialysis Patients.

INTRODUCTION: Though neutrophil/lymphocyte ratio (NLR) level appears to be related with stroke events in general population, its relationship with stroke in peritoneal dialysis (PD) patients is still uncertain. This study aims to investigate the association between NLR and the first occurrence of stroke in PD patients. METHODS: In this retrospective cohort study, 1507 PD patients were enrolled from four centers in China and stratified into tertiles of NLR levels. The incidence of the first occurrence of stroke was analyzed by Kaplan-Meier cumulative incidence curve among different NLR tertiles, competing risk analysis was used to calculate the incidence of the first occurrence of stroke in the presence of competing risk of other events, multivariable COX regression analysis was performed to estimate the hazard ratios (HRs) for the first occurrence of stroke, as well as forest plot was utilized to describe the relationship between NLR and the first occurrence of stroke in different subgroups. RESULTS: During follow-up, 84 new-onset stroke events were recorded. Kaplan-Meier cumulative incidence curves showed significant differences in the incidence of the first occurrence of stroke among three groups (log-rank test: P < .001). In competing risk analysis, the cumulative incidence curves for tertiles of NLR levels were highly significant for the first occurrence of stroke (P < .001), but they were not statistically different for the occurrence of other events. Compared to the lowest tertile of NLR level, the highest tertile was associated with increased risk of the first occurrence of stroke in the adjusted Cox model (HR = 2.39, 95% CI: 1.37 to 4.15; P < .05). As for forest plot, there was no interaction in all subgroups. CONCLUSION: High NLR was an independent risk factor for the first occurrence of stroke in PD patients.

Neutrophil to Lymphocyte Ratio Predicts Adverse Cardiovascular Outcome in Peritoneal Dialysis Patients Younger than 60 Years Old.

BACKGROUND: Neutrophil to lymphocyte ratio (NLR) is a new inflammatory marker; the relationship between NLR and adverse cardiovascular (CV) prognosis has been gradually emphasized in the general population. However, their association in peritoneal dialysis (PD) patients remains unclear. METHODS: From January 1, 2010, to May 31, 2017, a total of 1652 patients were recruited. NLR was categorized in triplicates: NLR ≤ 2.74, 2.74 < NLR ≤ 3.96, and NLR > 3.96. Kaplan-Meier cumulative incidence curve and multivariable COX regression analysis were used to determine the relationship between NLR and the incidence of adverse CV outcome, while a competitive risk model was applied to assess the effects of other outcomes on adverse CV prognosis. Besides, forest plot was investigated to analyze the adverse CV prognosis in different subgroups. RESULTS: During follow-up, 213 new-onset CV events and 153 CV disease (CVD) deaths were recorded. Multivariable COX regression models showed that the highest tertile of NLR level was associated with increased risk of CV events (HR = 1.39, 95%CI = 1.01-1.93, P = 0.046) and CVD mortality (HR = 1.81, 95%CI = 1.22-2.69, P = 0.003), while compared to the lowest tertile. Competitive risk models showed that the differences in CV event (P < 0.001) and CVD mortality (P = 0.004) among different NLR groups were still significant while excluding the effects of other outcomes. In subgroups, with each 1 increased in the NLR level, adjusted HR of new-onset CV event was 2.02 (95%CI = 1.26 - 3.23, P = 0.003) and CVD mortality was 2.98 (95%CI = 1.58 - 5.62, P = 0.001) in the younger group (age < 60 years). CONCLUSIONS: NLR is an independent risk factor for adverse CV prognosis in PD patients younger than 60 years old.

The metabolic role of PFKFB4 in androgen-independent growth in vitro and PFKFB4 expression in human prostate cancer tissue.

BACKGROUND: It is well known that androgen-deprivation therapy (ADT) can inevitably drive prostate cancer (PCa) cells into a castration-resistant state. According to the "Warburg effect", the metabolism of aggressive tumor cells increases significantly. The growth of cancer cells depends on glycolysis, which may be a potential target for cancer control. 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4) plays key roles in the proliferation and metastasis of PCa cells. However, there is very limited knowledge on the role of PFKFB4 in the conversion to castration resistance. The present study aimed to determine the changes in glucose consumption and PFKFB4 expression in LNCaP cells and androgen-independent LNCaP (LNCaP-AI) cells during the whole process of androgen-independent growth. Additionally, PFKFB4 expression in human PCa tissues was evaluated. METHODS: We established an androgen-independent LNCaP-AI cell line derived from LNCaP cells to mimic the traits of castration resistance in vitro. LNCaP-AI and LNCaP cells were cultured in the corresponding medium containing the same amount of glucose. At the end of experiments, the medium supernatant and blank medium were collected, and absorbance was measured. LNCaP-AI and LNCaP cells were harvested to detect PFKFB4 expression by Western blotting. Prostate tissue samples including PCa tissue, carcinoma-adjacent tissue and benign prostatic hyperplasia (BPH) tissue specimens were evaluated for PFKFB4 expression using immunohistochemistry. RESULTS: In 18 h supernatant samples, the glucose consumption and lactate secretion of LNCaP-AI cells were higher than those of LNCaP cells. The Western blot results indicated that PFKFB4 expression was increased in LNCaP-AI cells compared with LNCaP cells. Immunohistochemistry revealed that the expression of PFKFB4 in PCa tissue specimens was higher than that in BPH and adjacent tissue specimens. However, the differences in PCa tissue before and after ADT were not statistically significant. CONCLUSION: PFKFB4 may be associated with enhanced glycolysis during the androgen-independent growth of PCa cells in vitro. PFKFB4 may be a marker of PCa progression. Our results provide a rationale for further clinical investigation of PCa treatment focused on controlling PFKFB4 expression.