CCL19-CCR7-dependent reverse transendothelial migration of myeloid cells clears Chlamydia muridarum from the arterial intima.

Regions of the normal arterial intima predisposed to atherosclerosis are sites of ongoing monocyte trafficking and also contain resident myeloid cells with features of dendritic cells. However, the pathophysiological roles of these cells are poorly understood. Here we found that intimal myeloid cells underwent reverse transendothelial migration (RTM) into the arterial circulation after systemic stimulation of pattern-recognition receptors (PRRs). This process was dependent on expression of the chemokine receptor CCR7 and its ligand CCL19 by intimal myeloid cells. In mice infected with the intracellular pathogen Chlamydia muridarum, blood monocytes disseminated infection to the intima. Subsequent CCL19-CCR7-dependent RTM was critical for the clearance of intimal C. muridarum. This process was inhibited by hypercholesterolemia. Thus, RTM protects the normal arterial intima, and compromised RTM during atherogenesis might contribute to the intracellular retention of pathogens in atherosclerotic lesions.

Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

Nutrition-dependent juvenile hormone sensitivity promotes flight-muscle degeneration during the aphid dispersal-reproduction transition.

In insects, the loss of flight typically involves a dispersal-reproduction transition, but the underlying molecular mechanisms remain poorly understood. In the parthenogenetic pea aphid Acyrthosiphon pisum, winged females undergo flight-muscle degeneration after flight and feeding on new host plants. Similarly, topical application of a juvenile hormone (JH) mimic to starved aphids also induces flight-muscle degeneration. We found that feeding preferentially upregulated the expression of the JH receptor gene Met and a JH-inducible gene, Kr-h1, in the flight muscles, and, thus, enhanced tissue-specific JH sensitivity and signaling. RNAi-mediated knockdown of Kr-h1 prevented flight-muscle degeneration. Likewise, blocking nutritional signals by pharmacological inhibition of the target of rapamycin complex 1 (TORC1) impaired JH sensitivity of the flight muscles in feeding aphids and subsequently delayed muscle degeneration. RNA-sequencing analysis revealed that enhanced JH signaling inhibited the transcription of genes involved in the tricarboxylic acid cycle, likely resulting in reduction of the energy supply, mitochondrial dysfunction and muscle-fiber breakdown. This study shows that nutrient-dependent hormone sensitivity regulates developmental plasticity in a tissue-specific manner, emphasizing a relatively underappreciated mechanism of hormone sensitivity in modulating hormone signaling.

The pseudogene GBP1P1 suppresses influenza A virus replication by acting as a protein decoy for DHX9.

Recently, substantial evidence has demonstrated that pseudogene-derived long noncoding RNAs (lncRNAs) as regulatory RNAs have been implicated in basic physiological processes and disease development through multiple modes of functional interaction with DNA, RNA, and proteins. Here, we report an important role for GBP1P1, the pseudogene of guanylate-binding protein 1, in regulating influenza A virus (IAV) replication in A549 cells. GBP1P1 was dramatically upregulated after IAV infection, which is controlled by JAK/STAT signaling. Functionally, ectopic expression of GBP1P1 in A549 cells resulted in significant suppression of IAV replication. Conversely, silencing GBP1P1 facilitated IAV replication and virus production, suggesting that GBP1P1 is one of the interferon-inducible antiviral effectors. Mechanistically, GBP1P1 is localized in the cytoplasm and functions as a sponge to trap DHX9 (DExH-box helicase 9), which subsequently restricts IAV replication. Together, these studies demonstrate that GBP1P1 plays an important role in antagonizing IAV replication.IMPORTANCELong noncoding RNAs (lncRNAs) are extensively expressed in mammalian cells and play a crucial role as regulators in various biological processes. A growing body of evidence suggests that host-encoded lncRNAs are important regulators involved in host-virus interactions. Here, we define a novel function of GBP1P1 as a decoy to compete with viral mRNAs for DHX9 binding. We demonstrate that GBP1P1 induction by IAV is mediated by JAK/STAT activation. In addition, GBP1P1 has the ability to inhibit IAV replication. Importantly, we reveal that GBP1P1 acts as a decoy to bind and titrate DHX9 away from viral mRNAs, thereby attenuating virus production. This study provides new insight into the role of a previously uncharacterized GBP1P1, a pseudogene-derived lncRNA, in the host antiviral process and a further understanding of the complex GBP network.

Transcriptome-based molecular subtypes and differentiation hierarchies improve the classification framework of acute myeloid leukemia.

The current classification of acute myeloid leukemia (AML) relies largely on genomic alterations. Robust identification of clinically and biologically relevant molecular subtypes from nongenomic high-throughput sequencing data remains challenging. We established the largest multicenter AML cohort (n = 655) in China, with all patients subjected to RNA sequencing (RNA-Seq) and 619 (94.5%) to targeted or whole-exome sequencing (TES/WES). Based on an enhanced consensus clustering, eight stable gene expression subgroups (G1-G8) with unique clinical and biological significance were identified, including two unreported (G5 and G8) and three redefined ones (G4, G6, and G7). Apart from four well-known low-risk subgroups including PML::RARA (G1), CBFB::MYH11 (G2), RUNX1::RUNX1T1 (G3), biallelic CEBPA mutations or -like (G4), four meta-subgroups with poor outcomes were recognized. The G5 (myelodysplasia-related/-like) subgroup enriched clinical, cytogenetic and genetic features mimicking secondary AML, and hotspot mutations of IKZF1 (p.N159S) (n = 7). In contrast, most NPM1 mutations and KMT2A and NUP98 fusions clustered into G6-G8, showing high expression of HOXA/B genes and diverse differentiation stages, from hematopoietic stem/progenitor cell down to monocyte, namely HOX-primitive (G7), HOX-mixed (G8), and HOX-committed (G6). Through constructing prediction models, the eight gene expression subgroups could be reproduced in the Cancer Genome Atlas (TCGA) and Beat AML cohorts. Each subgroup was associated with distinct prognosis and drug sensitivities, supporting the clinical applicability of this transcriptome-based classification of AML. These molecular subgroups illuminate the complex molecular network of AML, which may promote systematic studies of disease pathogenesis and foster the screening of targeted agents based on omics.

Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases.

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of T cell progenitors, known to be a heterogeneous disease in pediatric and adult patients. Here we attempted to better understand the disease at the molecular level based on the transcriptomic landscape of 707 T-ALL patients (510 pediatric, 190 adult patients, and 7 with unknown age; 599 from published cohorts and 108 newly investigated). Leveraging the information of gene expression enabled us to identify 10 subtypes (G1­G10), including the previously undescribed one characterized by GATA3 mutations, with GATA3R276Q capable of affecting lymphocyte development in zebrafish. Through associating with T cell differentiation stages, we found that high expression of LYL1/LMO2/SPI1/HOXA (G1­G6) might represent the early T cell progenitor, pro/precortical/cortical stage with a relatively high age of disease onset, and lymphoblasts with TLX3/TLX1 high expression (G7­G8) could be blocked at the cortical/postcortical stage, while those with high expression of NKX2-1/TAL1/LMO1 (G9­G10) might correspond to cortical/postcortical/mature stages of T cell development. Notably, adult patients harbored more cooperative mutations among epigenetic regulators, and genes involved in JAK-STAT and RAS signaling pathways, with 44% of patients aged 40 y or above in G1 bearing DNMT3A/IDH2 mutations usually seen in acute myeloid leukemia, suggesting the nature of mixed phenotype acute leukemia.

The novel TERF2::PDGFRB fusion gene enhances tumorigenesis via PDGFRB/STAT5 signalling pathways and sensitivity to TKI in ph-like ALL.

Patients with Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like ALL) often face a grim prognosis, with PDGFRB gene fusions being commonly detected in this subgroup. Our study has unveiled a newfound fusion gene, TERF2::PDGFRB, and we have found that patients carrying this fusion gene exhibit sensitivity to dasatinib. Ba/F3 cells harbouring the TERF2::PDGFRB fusion display IL-3-independent cell proliferation through activation of the p-PDGFRB and p-STAT5 signalling pathways. These cells exhibit reduced apoptosis and demonstrate sensitivity to imatinib in vitro. When transfused into mice, Ba/F3 cells with the TERF2::PDGFRB fusion gene induce tumorigenesis and a shortened lifespan in cell-derived graft models, but this outcome can be improved with imatinib treatment. In summary, we have identified the novel TERF2::PDGFRB fusion gene, which exhibits oncogenic potential both in vitro and in vivo, making it a potential therapeutic target for tyrosine kinase inhibitors (TKIs).

Simultaneous Multi-miRNA Detection in Urinary Small Extracellular Vesicles Using Target-Triggered Locked Hairpin DNA-Functionalized Au Nanoprobes for Systemic Lupus Erythematosus Diagnosis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multiorgan involvement and complex clinical manifestations, leading to cumbersome diagnostic processes. MicroRNAs (miRNAs) in small extracellular vesicles (sEVs) have emerged as promising biomarkers for liquid biopsy. Herein, we constructed a simple multi-miRNA detection platform based on target-triggered locked hairpin DNA-functionalized Au nanoprobes (AuNP@LH) as a simple and noninvasive tool for the diagnosis and classification of SLE. The nanoprobes were prepared by modifying locked hairpin DNA designed for target miRNAs on gold nanoparticles. In the presence of target miRNAs, target-triggered hairpin assembly amplification was induced, and then fluorophore-labeled bolt DNA was released, resulting in a fluorescence signal responsive to miRNA concentration. Benefiting from the enzyme-free amplification strategy, the limits of detection (LOD) of three miRNA biomarkers for SLE were 19 pM for microRNA-146a, 66 pM for microRNA-29c, and 19 pM for microRNA-150. The proposed probes have been successfully applied to simultaneously detect multiple miRNAs in urinary sEVs from patients diagnosed with SLE and healthy controls, which exhibited good practicability in SLE diagnosis with the area under curve (AUC) of the receiver characteristic curve reaching 1.00. Furthermore, SLE patients with different disease severity can be differentiated with 81.2% accuracy. Predictably, with the advantages of low cost, rapidity, high sensitivity, and noninvasiveness, our multi-miRNA detection platform is a potential tool for multiple miRNA analysis and related clinical applications.

Bootstrapping Deconfined Quantum Tricriticality.

The paradigmatic example of deconfined quantum criticality is the Neel to valence bond solid phase transition. The continuum description of this transition is the N=2 case of the CP^{N-1} model, which is a field theory of N complex scalars in 3D coupled to an Abelian gauge field with SU(N)×U(1) global symmetry. Lattice studies and duality arguments suggest the global symmetry of the CP^{1} model is enhanced to SO(5). We perform a conformal bootstrap study of SO(5) invariant fixed points with one relevant SO(5) singlet operator, which would correspond to two relevant SU(2)×U(1) singlets, i.e., a tricritical point. We find that the bootstrap bounds are saturated by four different predictions from the large N computation of monopole operator scaling dimensions, which were recently shown to be very accurate even for small N. This suggests that the Neel to valence bond solid phase transition is described by this bootstrap bound, which predicts that the second relevant singlet has dimension ≈2.36.

Two Birds with One Stone: Polymerized Thermally Activated Delayed Fluorescence Small Molecules.

Thermally activated delayed fluorescence (TADF) polymers show a great potential in low-cost, large-area and flexible full-color flat-panel displays. One of the most promising design rules is based on TADF+Linker, where a small molecular TADF unit is bonded to each other by a simple linker. Unlike the expensive vacuum deposition for small molecules, these polymerized TADF small molecules (Poly-TADF-SMs) are capable of cost-effective solution processing. Meanwhile, the good luminescent property of small molecular TADF emitters can be well inherited by Poly-TADF-SMs so as to bridge the efficiency gap between small molecules and polymers. Herein, we will highlight the recent progress of Poly-TADF-SMs, together with emphasis on their molecular design, photophysical and electroluminescence properties.

Factors Influencing Plasma Concentrations of Valproic Acid in Pediatric Patients With Epilepsy and the Clinical Significance of CYP2C9 Genotypes in Personalized Valproic Acid Therapy.

BACKGROUND: The aim of this study was to investigate the factors affecting plasma valproic acid (VPA) concentration in pediatric patients with epilepsy and the clinical significance of CYP2C9 gene polymorphisms in personalized dosing using therapeutic drug monitoring and pharmacogenetic testing. METHODS: The medical records of children with epilepsy who underwent therapeutic drug monitoring at our institution between July 2022 and July 2023 and met the inclusion criteria were reviewed. Statistical analysis was performed to determine whether age, sex, blood ammonia, liver function, kidney function, and other characteristics affected the concentration-to-dose ratio of VPA (CDRV) in these patients. To investigate the effect of CYP2C9 polymorphisms on CDRV, DNA samples were collected from patients and the CYP2C9 genotypes were identified using real-time quantitative PCR. RESULTS: The mean age of 208 pediatric patients with epilepsy was 5.50 ± 3.50 years. Among these patients, 182 had the CYP2C9 *1/*1 genotype, with a mean CDRV (mcg.kg/mL.mg) of 2.64 ± 1.46, 24 had the CYP2C9 *1/*3 genotype, with a mean CDRV of 3.28 ± 1.74, and 2 had the CYP2C9 *3/*3 genotype, with a mean CDRV of 6.46 ± 3.33. There were statistical differences among these 3 genotypes ( P < 0.05). The CDRV in these patients were significantly influenced by age, aspartate aminotransferase, total bilirubin, direct bilirubin, globulin, albumin/globulin ratio, prealbumin, creatinine, and CYP2C9 polymorphisms. In addition, multivariate linear regression analysis identified total bilirubin, direct bilirubin, and CYP2C9 polymorphisms as independent risk factors for high CDRV. CONCLUSIONS: Liver problems and mutations in the CYP2C9 gene increase VPA levels. This underscores the importance of considering these factors when prescribing VPA to children with epilepsy, thereby enhancing the safety and efficacy of the therapy.

CXCL9/CXCL10 as biomarkers the monitoring of treatment responses in Pulmonary TB patients: a systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) remains a persistent threat to global public health and traditional treatment monitoring approaches are limited by their potential for contamination and need for timely evaluation. Therefore, new biomarkers are urgently required for monitoring the treatment efficacy of TB. METHODS: This study aimed to elucidate the levels of CXCL10 and CXCL9 in pulmonary TB patients who underwent anti-TB treatment. The data was acquired from five databases, including PubMed, Ovid, Web of Science, Embase, and the Cochrane Library. A meta-analysis of CXCL10 data from all time points was conducted. Furthermore, a trend meta-analysis of temporal data of CXCL10 and CXCL9 from multiple time points was also performed. RESULTS: It was revealed that patients who responded poorly to anti-TB treatment had higher serum levels relative to those who responded well (SMD: 1.23, 95% CI: -0.37-2.84) at the end of intensive treatment (2 months). Furthermore, heterogeneity was observed in these results, which might be because patients with a prior history of TB and different treatment monitoring methods than those selected in this study were also included. The analysis of alterations in CXCL10 and CXCL9 levels since the last collection time points indicated that their levels reduced with time. CONCLUSION: In summary, the study revealed that reductions in CXCL10 levels during the first two months of anti-TB treatment are correlated with treatment responses. Furthermore, decreasing levels of CXCL9 during the treatment suggest that it may also serve as a biomarker with a similar value to CXCL10. Future in-depth studies are thus warranted to further probe the relevance of CXCL10 and CXCL9 in monitoring the treatment efficacy of TB.

NLRP4E regulates actin cap formation through SRC and CDC42 during oocyte meiosis.

BACKGROUND: Members of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing (NLRP) family regulate various physiological and pathological processes. However, none have been shown to regulate actin cap formation or spindle translocation during the asymmetric division of oocyte meiosis I. NLRP4E has been reported as a candidate protein in female fertility, but its function is unknown. METHODS: Immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were employed to examine the localization and expression levels of NLRP4E and related proteins in mouse oocytes. small interfering RNA (siRNA) and antibody transfection were used to knock down NLRP4E and other proteins. Immunoprecipitation (IP)-mass spectrometry was used to identify the potential proteins interacting with NLRP4E. Coimmunoprecipitation (Co-IP) was used to verify the protein interactions. Wild type (WT) or mutant NLRP4E messenger RNA (mRNA) was injected into oocytes for rescue experiments. In vitro phosphorylation was employed to examine the activation of steroid receptor coactivator (SRC) by NLRP4E. RESULTS: NLRP4E was more predominant within oocytes compared with other NLRP4 members. NLRP4E knockdown significantly inhibited actin cap formation and spindle translocation toward the cap region, resulting in the failure of polar body extrusion at the end of meiosis I. Mechanistically, GRIN1, and GANO1 activated NLRP4E by phosphorylation at Ser429 and Thr430; p-NLRP4E is translocated and is accumulated in the actin cap region during spindle translocation. Next, we found that p-NLRP4E directly phosphorylated SRC at Tyr418, while p-SRC negatively regulated p-CDC42-S71, an inactive form of CDC42 that promotes actin cap formation and spindle translocation in the GTP-bound form. CONCLUSIONS: NLRP4E activated by GRIN1 and GANO1 regulates actin cap formation and spindle translocation toward the cap region through upregulation of p-SRC-Tyr418 and downregulation of p-CDC42-S71 during meiosis I.

Associations between different insulin resistance indices and the risk of all-cause mortality in peritoneal dialysis patients.

BACKGROUND: Insulin resistance (IR) is prevalent in individuals undergoing peritoneal dialysis (PD) and is related to increased susceptibility to coronary artery disease and initial peritonitis. In recent investigations, correlations have been found between indices of IR and the incidence of all-cause mortality in various populations. However, such correlations have not been detected among individuals undergoing PD. Hence, the present study's aim was to explore the connections between IR indices and the incidence of all-cause mortality in PD patients. METHODS: Peritoneal dialysis patients (n = 1736) were recruited from multiple PD centres between January 2010 and December 2021. Cox proportional hazards and restricted cubic spline regression models were used to evaluate the connections between the triglyceride-glucose (TyG) index, triglyceride-glucose/body mass index (TyG-BMI), and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and the occurrence of all-cause mortality. All three IR indices were integrated into the same model to assess the predictive stability. Furthermore, a forest plot was employed to display the findings of the subgroup analysis of PD patients. RESULTS: Overall, 378 mortality events were recorded during a median follow-up time of 2098 days. Among PD patients, a higher TyG index, TyG-BMI, and TG/HDL-C ratio were identified as independent risk factors for all-cause mortality according to Cox proportional hazards analyses (hazard ratio (HR) 1.588, 95% confidence interval (CI) 1.261-2.000; HR 1.428, 95% CI 1.067-1.910; HR 1.431, 95% CI 1.105-1.853, respectively). In a model integrating the three IR indices, the TyG index showed the highest predictive stability. According to the forest plot for the TyG index, no significant interactions were observed among the subgroups. CONCLUSION: Significant associations were found between the TyG index, TyG-BMI, and TG/HDL-C ratio and the incidence of all-cause mortality among PD patients. The TyG index may be the most stable of the three surrogate IR markers. Finally, a correlation was identified between IR and the risk of all-cause mortality in patients undergoing PD.

YME1L-mediated mitophagy protects renal tubular cells against cellular senescence under diabetic conditions.

BACKGROUND: The senescence of renal tubular epithelial cells (RTECs) is crucial in the progression of diabetic kidney disease (DKD). Accumulating evidence suggests a close association between insufficient mitophagy and RTEC senescence. Yeast mitochondrial escape 1-like 1 (YME1L), an inner mitochondrial membrane metalloprotease, maintains mitochondrial integrity. Its functions in DKD remain unclear. Here, we investigated whether YME1L can prevent the progression of DKD by regulating mitophagy and cellular senescence. METHODS: We analyzed YME1L expression in renal tubules of DKD patients and mice, explored transcriptomic changes associated with YME1L overexpression in RTECs, and assessed its impact on RTEC senescence and renal dysfunction using an HFD/STZ-induced DKD mouse model. Tubule-specific overexpression of YME1L was achieved through the use of recombinant adeno-associated virus 2/9 (rAAV 2/9). We conducted both in vivo and in vitro experiments to evaluate the effects of YME1L overexpression on mitophagy and mitochondrial function. Furthermore, we performed LC-MS/MS analysis to identify potential protein interactions involving YME1L and elucidate the underlying mechanisms. RESULTS: Our findings revealed a significant decrease in YME1L expression in the renal tubules of DKD patients and mice. However, tubule-specific overexpression of YME1L significantly alleviated RTEC senescence and renal dysfunction in the HFD/STZ-induced DKD mouse model. Moreover, YME1L overexpression exhibited positive effects on enhancing mitophagy and improving mitochondrial function both in vivo and in vitro. Mechanistically, our LC-MS/MS analysis uncovered a crucial mitophagy receptor, BCL2-like 13 (BCL2L13), as an interacting partner of YME1L. Furthermore, YME1L was found to promote the phosphorylation of BCL2L13, highlighting its role in regulating mitophagy. CONCLUSIONS: This study provides compelling evidence that YME1L plays a critical role in protecting RTECs from cellular senescence and impeding the progression of DKD. Overexpression of YME1L demonstrated significant therapeutic potential by ameliorating both RTEC senescence and renal dysfunction in the DKD mice. Moreover, our findings indicate that YME1L enhances mitophagy and improves mitochondrial function, potentially through its interaction with BCL2L13 and subsequent phosphorylation. These novel insights into the protective mechanisms of YME1L offer a promising strategy for developing therapies targeting DKD.

Association between systemic immune inflammation Index and all-cause mortality in incident peritoneal dialysis-treated CKD patients: a multi-center retrospective cohort study.

BACKGROUND: Chronic inflammatory disorders in peritoneal dialysis (PD) contribute to the adverse clinical outcome. Systemic immune inflammation index (SII) is the novel and convenient measurement that is positively associated with various diseases. However, scarce is known regarding the association between SII with all-cause mortality among PD patients. METHODS: In this multi-center retrospective cohort study, 1,677 incident patients with PD were enrolled. Eligible patients were stratified into groups based on SII level: tertile 1(< 456.76), tertile 2(456.76 to 819.03), and tertile 3(> 819.03). The primary endpoint was the all-cause mortality. Both Cox regression analysis and competing risk models were used to examine the association between SII and all-cause mortality. Subgroup analysis was performed to assess the influence of the SII tertiles on all-cause mortality in different subgroups. RESULTS: During the follow-up period of 30.5 ± 20.0 months, 26.0% (437/1,677) patients died, of whom the SII tertile 3 group accounted for 39.1% (171/437) of the deaths. Patients in the SII tertile 3 group had a higher all-cause mortality rate than patients in the SII tertile 1 and 2 groups (log-rank = 13.037, P < 0.001). The SII tertile 3 group was significantly associated with 80% greater risk (95% confidence interval:1.13 to 2.85; P = 0.013) compared with the SII tertile 1 group in multivariable Cox regression analysis. The competing risk model also indicated that the relationship between SII tertiles and all-cause mortality remains (subdistribution hazard ratio: 1.86; 95% confidence interval: 1.15 to 2.02, P = 0.011). Furthermore, the relationship between the log-transformed SII and all-cause mortality in patients with PD was nearly linear (P = 0.124). CONCLUSION: A close relationship was observed between the SII and all-cause mortality in patients undergoing PD, suggesting that more attention should be paid to the SII, which is a convenient and effective measurement in clinical practice.

Platelet-to-albumin ratio: a potential biomarker for predicting all-cause and cardiovascular mortality in patients undergoing peritoneal dialysis.

BACKGROUND: Although peritoneal dialysis (PD) is an efficient therapy for renal replacement, the long-term survival rate of patients undergoing PD remains low. The platelet-to-albumin ratio (PAR), recently identified as a parameter of inflammatory and nutritional status, is associated with an adverse prognosis for various diseases. However, the association between the serum PAR and prognosis of patients undergoing PD is poorly understood. This study aimed to evaluate whether the PAR is a reliable predictor of cardiovascular disease (CVD) and all-cause mortality in patients undergoing PD. METHODS: This multicenter cohort study enrolled patients undergoing PD from January 1, 2009, to September 30, 2018. The patients were divided into four groups according to the quartiles of their baseline PAR. The primary endpoint was all-cause and CVD-related mortality. Cox proportional hazard models were used to determine the association between the PAR and all-cause or CVD-related mortality. The receiver operating characteristic (ROC) curve was utilized to compare the performance among PAR and other inflammatory indicators. C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were applied to examine the incremental prognostic value of PAR compared with baseline model for predicting all-cause and CVD mortality. RESULTS: A total of 2825 patients were included. During the follow-up period of 47.5 ± 28.3 months, 747 (26.4%) mortality cases were observed, of which 415 (55.6%) were CVD-related. Compared with the Q1 (PAR < 4.43), placement in Q4 (PAR > 7.27) was associated with an increased risk of all-cause mortality and CVD mortality (p < 0.001). The adjusted restricted cubic spline analysis indicated that the relationship of the PAR with all-cause and cardiovascular mortality was linear (p for nonlinearity = 0.289 and 0.422, respectively). No positive correlations were shown in the interaction tests. PAR exhibited superior predictive value for mortality compared to other inflammatory indicators, with a respective AUC value of 0.611 (P < 0.001) for all-cause mortality and 0.609 (P < 0.001) for cardiovascular mortality. According to the C-statistic, continuous NRI and IDI, the addition of PAR to the baseline model yielded a moderate but significant improvement in outcome prediction. CONCLUSIONS: The PAR is an independent prognostic factor associated with all-cause and cardiovascular mortality in patients undergoing PD.

Electronic Health Literacy Scale-Web3.0 for Older Adults with Noncommunicable Diseases: Validation Study.

BACKGROUND: In the current digital era, eHealth literacy plays an indispensable role in health care and self-management among older adults with noncommunicable diseases (NCDs). Measuring eHealth literacy appropriately and accurately ensures the successful implementation and evaluation of pertinent research and interventions. However, existing eHealth literacy measures focus mainly on individuals' abilities of accessing and comprehending eHealth information (Web1.0), whereas the capabilities for web-based interaction (Web2.0) and using eHealth information (Web3.0) have not been adequately evaluated. OBJECTIVE: This study aimed to examine the reliability, validity, and measurement invariance of the eHealth Literacy Scale-Web3.0 (eHLS-Web3.0) among older adults with NCDs. METHODS: A total of 642 Chinese older adults with NCDs (mean age 65.78, SD 3.91 years; 55.8% female) were recruited in the baseline assessment, of whom 134 (mean age 65.63, SD 3.99 years; 58.2% female) completed the 1-month follow-up assessment. Baseline measures included the Chinese version of the 24-item 3D eHLS-Web3.0, the Chinese version of the 8-item unidimensional eHealth Literacy Scale (eHEALS), and demographic information. Follow-up measures included the 24-item eHLS-Web3.0 and accelerometer-measured physical activity and sedentary behavior. A series of statistical analyses, for example, Cronbach α, composite reliability coefficient (CR), confirmatory factor analysis (CFA), and multigroup CFA, were performed to examine the internal consistency and test-retest reliabilities, as well as the construct, concurrent, convergent, discriminant, and predictive validities, and the measurement invariance of the eHLS-Web3.0 across gender, education level, and residence. RESULTS: Cronbach α and CR were within acceptable ranges of 0.89-0.94 and 0.90-0.97, respectively, indicating adequate internal consistency of the eHLS-Web3.0 and its subscales. The eHLS-Web3.0 also demonstrated cross-time stability, with baseline and follow-up measures showing a significant intraclass correlation of 0.81-0.91. The construct validity of the 3D structure model of the eHLS-Web3.0 was supported by confirmatory factor analyses. The eHLS-Web3.0 exhibited convergent validity with an average variance extracted value of 0.58 and a CR value of 0.97. Discriminant validity was supported by CFA results for a proposed 4-factor model integrating the 3 eHLS-Web3.0 subscales and eHEALS. The predictive validity of the eHLS-Web3.0 for health behaviors was supported by significant associations of the eHLS-Web3.0 with light physical activity (ß=.36, P=.004), moderate to vigorous physical activity (ß=.49, P<.001), and sedentary behavior (ß=-.26, P=.002). Finally, the measurement invariance of the eHLS-Web3.0 across gender, education level, and residence was supported by the establishment of configural, metric, strong, and strict invariances. CONCLUSIONS: The present study provides timely empirical evidence on the reliability, validity, and measurement invariance of the eHLS-Web3.0, suggesting that the 24-item 3D eHLS-Web3.0 is an appropriate and valid tool for measuring eHealth literacy among older adults with NCDs within the Web3.0 sphere.

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.