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Abstract 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 7.27) was associated with an increased risk of all-cause mortality and CVD mortality (p

Abstract 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.

Purpose Gastrointestinal bleeding is an important gastrointestinal complication among peritoneal dialysis patients and correlated with a higher risk of mortality. Increased uric acid levels are a significant complication for peritoneal dialysis patients and have been associated with an increased risk of hemorrhagic stroke. The objective of the present study was to investigate the relationship between serum uric acid levels and gastrointestinal bleeding in peritoneal dialysis patients.Methods A total of 2498 peritoneal dialysis patients were recruited. Based on the optimal uric acid cutoff value, two groups of patients were divided. We constructed a propensity-score-matched population of 1762 patients by matching sex, age, and body mass index. Survival outcomes between the two groups were compared using adjusted Kaplan–Meier curves. We constructed the restricted cubic splines regression to assess the correlation between levels of uric acid and gastrointestinal bleeding. A multivariate Cox proportional hazards regression was performed to test whether higher levels of uric acid are an independent risk factor for gastrointestinal bleeding. We performed a forest plot to show interaction effects in different subgroups.Results According to restricted cubic splines regression, uric acid levels were positively correlated with the risk of gastrointestinal bleeding events. After adjusted different confounding factors, patients with high levels of uric acid were prone to experience gastrointestinal bleeding (HR 1.868, 95%CI 1.001–3.486). In subgroups, the interaction between higher levels of uric acid and utilizing proton pump inhibitors was significant (P for interaction = 0.034). Further research found that taking proton pump inhibitors could decrease the risk of gastrointestinal bleeding in peritoneal dialysis patients accompanied high levels of uric acid.Conclusion The baseline high levels of uric acid are an independent risk factor for gastrointestinal bleeding in patients undergoing peritoneal dialysis.

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

Abstract Background Progressive peritoneal fibrosis is a worldwide public health concern impacting patients undergoing peritoneal dialysis (PD), yet there is no effective treatment. Our previous study revealed that a novel compound, micheliolide (MCL) inhibited peritoneal fibrosis in mice. However, its mechanism remains unclear. Brahma-related gene 1 (BRG1) is a key contributor to organ fibrosis, but its potential function in PD-related peritoneal fibrosis and the relationship between MCL and BRG1 remain unknown. Methods The effects of MCL on BRG1-induced fibrotic responses and TGF-β1-Smads pathway were examined in a mouse PD model and in vitro peritoneal mesothelial cells. To investigate the targeting mechanism of MCL on BRG1, coimmunoprecipitation, MCL-biotin pulldown, molecular docking and cellular thermal shift assay were performed. Results BRG1 was markedly elevated in a mouse PD model and in peritoneal mesothelial cells cultured in TGF-β1 or PD fluid condition. BRG1 overexpression in vitro augmented fibrotic responses and promoted TGF-β1-increased-phosphorylation of Smad2 and Smad3. Meanwhile, knockdown of BRG1 diminished TGF-β1-induced fibrotic responses and blocked TGF-β1-Smad2/3 pathway. MCL ameliorated BRG1 overexpression-induced peritoneal fibrosis and impeded TGF-β1-Smad2/3 signaling pathway both in a mouse PD model and in vitro. Mechanically, MCL impeded BRG1 from recognizing and attaching to histone H3 lysine 14 acetylation by binding to the asparagine (N1540) of BRG1, in thus restraining fibrotic responses and TGF-β1-Smad2/3 signaling pathway. After the mutation of N1540 to alanine (N1540A), MCL was unable to bind to BRG1 and thus, unsuccessful in suppressing BRG1-induced fibrotic responses and TGF-β1-Smad2/3 signaling pathway. Conclusion Our research indicates that BRG1 may be a crucial mediator in peritoneal fibrosis and MCL targeting N1540 residue of BRG1 may be a novel therapeutic strategy to combat PD-related peritoneal fibrosis.

Lung cancer is one of the most malignant diseases and a major contributor to cancer-related deaths worldwide due to the deficiency of early diagnosis and effective therapy that are of great importance for patient prognosis and quality of life. Over the past decade, the advent of clustered regularly interspaced short palindromic repeats/CRISPR associated protein (CRISPR/Cas) system has significantly propelled the progress of both fundamental research and clinical trials of lung cancer. In this review, we review the current applications of the CRISPR/Cas system in diagnosis, target identification, and treatment resistance of lung cancer. Furthermore, we summarize the development of lung cancer animal models and delivery methods based on CRISPR system, providing novel insights into clinical diagnosis and treatment strategies of lung cancer.

Background Serum uric acid to serum creatinine ratio (SUA/Scr) has emerged as a new biomarker, which is significantly associated with several metabolic diseases. However, no study has investigated the association between SUA/Scr and mortality among patients on continuous ambulatory peritoneal dialysis (CAPD).Methods In this multicenter retrospective cohort study, we enrolled CAPD patients in eight tertiary hospitals in China from 1 January 2005 to 31 May 2021. Cox proportional hazard models were used to determine the relationship between SUA/Scr and mortality.Results A total of 2480 patients were included; the mean age was 48.9 ± 13.9 years and 56.2% were males. During 12648.0 person-years of follow-up, 527 (21.3%) patients died, of which 267 (50.7%) deaths were caused by cardiovascular disease. After multivariable adjustment for covariates, per unit increase in SUA/Scr was associated with a 62.9% (HR, 1.629 (95% confidence interval (CI) 1.420–1.867)) and 73.0% (HR, 1.730 (95% CI 1.467–2.041)) higher risk of all-cause and cardiovascular mortality. Results were similar when categorized individuals by SUA/Scr quartiles. Compared with the lowest quartile of SUA/Scr, the highest and the second highest quartile of SUA/Scr had a 2.361-fold (95% CI 1.810–3.080) and 1.325-fold (95% CI 1.003–1.749) higher risk of all-cause mortality, as well as a 3.701-fold (95% CI 2.496–5.489) and 2.074-fold (95% CI 1.387–3.100) higher risk of cardiovascular mortality. Multivariable-adjusted spline regression models showed nonlinear association of SUA/Scr with mortality in CAPD patients.Conclusions Higher levels of SUA/Scr were associated with higher risk of all-cause and cardiovascular mortality in CAPD patients.

AbstractBackground The glucose-to-lymphocyte ratio (GLR), a glucose metabolism and systemic inflammatory response parameter, is associated with an adverse prognosis for various diseases. However, the association between serum GLR and prognosis in patients undergoing peritoneal dialysis (PD) is poorly understood.Methods In this multi-center cohort study, 3236 PD patients were consecutively enrolled between 1 January 2009 and 31 December 2018. Patients were divided into four groups according to the quartiles of baseline GLR levels (Q1: GLR ≤ 2.91, Q2:2.91

AbstractBackground Immune-inflammatory biomarkers (IIBs) have been shown to be correlated with prognosis in patients undergoing peritoneal dialysis (PD). In this study, we aimed to evaluate the relationship between a novel comprehensive biomarker, the pan-immune-inflammation value (PIV), and the prognosis of patients undergoing PD.Methods We retrospectively analyzed data from a multicenter, large-sample PD database. PIV was calculated as (neutrophil count × platelet count × monocyte count)/lymphocyte count. The prognostic endpoints in this study were all-cause death all-cause, cardiovascular disease (CVD) and infection-related death. The Kaplan–Meier method, a Cox proportional hazards regression, Fine–Gray competing risk model, smooth curve, and subgroup analysis were used to analyze the independent relationship between PIV and the prognosis of patients undergoing PD.Results A total of 2796 cases of PD were included, and the study population was divided into Tertiles 1, 2, and 3, according to the tertiles of baseline PIVs. After adjusting for multiple model factors, patients in the Tertile 3 group had a significantly higher risk of all-cause death, CVD death and infection-related death compared with patients with PIV in the Tertile 1 group. Interaction tests showed no positive correlations for subgroup parameters. Regarding all-cause death, compared with the lowest tertile, the multivariable-adjusted hazard ratios (95% confidence intervals) of the highest and middle tertiles were 1.55 (1.25–1.94) and 1.77 (1.43–2.19), respectively; PIV (log2 processing) was associated with 17% excess of mortality in the continuous model.Conclusions A high PIV at baseline was significantly associated with an increased risk of deaths due to all-causes, CVD and infection in patients undergoing PD.

Abstract Background Total cholesterol is inversely associated with mortality in dialysis patients, which seems implausible in real-world clinical practice. May there be an optimal range of total cholesterol associated with a lower mortality risk? We aimed to evaluate the optimal range for peritoneal dialysis (PD) patients. Methods We conducted a retrospective real-world cohort study of 3565 incident PD patients from five PD centers between January 1, 2005, and May 31, 2020. Baseline variables were collected within one week before the start of PD. The associations between total cholesterol and mortality were examined using cause-specific hazard models. Results 820 (23.0%) patients died, including 415 cardiovascular deaths, during the follow-up period. Restricted spline plots showed a U-curved association of total cholesterol with mortality. Compared with the reference range (4.10–4.50 mmol/L), high levels of total cholesterol (> 4.50 mmol/L) were associated with increased risks of all-cause (hazard ratio [HR] 1.35, 95% confidence index [CI] 1.08–1.67) and cardiovascular mortality (HR 1.38, 95% CI 1.09–1.87). Similarly, compared with the reference range, low levels of total cholesterol (

Objectives The global mortality rate from chronic kidney disease (CKD) has increased over the past two decades. Typically, peritoneal dialysis (PD) remains a useful alternative treatment for end-stage renal disease. Cardiovascular disease (CVD) is the main complication in PD patients. In terms of prognosis, it is reported that platelet distribution width (PDW) can predict adverse CVD events. However, the relationship between PDW and new-onset CVD in PD patients is not clear. This study aimed to explore the relationship between PDW and new-onset CVD in PD patients.Methods This was a retrospective cohort study, from 4 July 2005 to 31 December 2019, and a total of 1557 patients were recruited. PDW was respectively categorized into two groups: PDW ≤13.2 fL and PDW >13.2 fL. The primary outcome was a new-onset CVD event. Cox proportional hazards models were performed to assess the hazard ratio (HR). Receiver-operating characteristic (ROC) curves were applied to evaluate the predictive accuracy of the PDW on CVD events.Results During follow-up, 114 new-onset CVD events were recorded. Cox proportional hazards models showed a higher risk of CVD events in patients with high PDW (HR = 1.862 95%CI 1.205–2.877, p = 0.005). Kaplan–Meier cumulative incidence curves showed the risk of the first occurrence of CVD events was greater in the high PDW group (p = 0.006).Conclusions High PDW is associated with new-onset cardiovascular disease events in PD 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

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

Abstract Background New lipid-lowering therapy at the start of dialysis and measurement of lipid parameters over the follow-up period is not recommended in dialysis patients, which seems unappropriated in clinical practice. We aimed to examine the effect of hyperlipidemia on mortality in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Methods A retrospective cohort study was performed, including 2939 incident CAPD patients from five dialysis facilities between January 1, 2005, and December 31, 2018. The primary outcome was all-cause mortality. The association between hyperlipidemia at the start of CAPD and all-cause mortality was evaluated using Cox proportional hazards regression. Results Of 2939 with a median age of 50.0 (interquartile range, 39.0–61.0), 1697 (57.7%) were men, 533 (18.1%) had hyperlipidemia, 549 (18.7%) had diabetes mellitus, 1915 (65.2%) had hypertension, and 410 (14.0%) had a history of CVD. During the median follow-up period of 35.1 months, 519 (17.7%) died, including 402 (16.7%, 47.4/1000 patient-years) in the non-hyperlipidemia group and 117 (22.0%, 71.1/1000 patient-years) in the hyperlipidemia group. Over the overall follow-up period, patients with hyperlipidemia had an equally high risk of all-cause mortality throughout follow-up as those without hyperlipidemia ([HR] 1.04, 95% confidence interval [CI] 0.83 to 1.31). However, from the 48-month follow-up onwards, hyperlipidemia was associated with a 2.26 (95% CI 1.49 to 3.43)-time higher risk of all-cause mortality than non-hyperlipidemia. Hypertension modified the association between hyperlipidemia and all-cause mortality (P for interaction

Aim: The aim of this study was to investigate the role and mechanism of long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3)-205 in renal inflammation and fibrosis in diabetic nephropathy (DN). Materials and Methods: lncRNA microarray profiling was used to examine differentially expressed lncRNAs of kidney tissues in db/db mice compared to db/m mice. Mouse mesangial cells (mMCs) were cultured in vitro with advanced glycation end products (AGEs) via transfection with lncRNA MEG3-205 siRNAs or plasmids. The role of lncRNA MEG3-205 in vivo was examined in db/db mice treated with long-acting lncRNA MEG3-205 siRNA. The interaction between lncRNA MEG3-205 and let-7a was investigated using luciferase assay and RNA immunoprecipitation assay. Results: lncRNA MEG3-205 was markedly upregulated in renal tissues of db/db mice, DN patients, and AGEs-treated mesangial cells. Overexpression of lncRNA MEG3-205 promoted the secretion of pro-inflammatory cytokines and synthesis of extracellular matrix proteins in mesangial cells. Both lncRNA MEG3-205 and myeloid differentiation primary-response protein 88 (MyD88) could bind to let-7a, and lncRNA MEG3-205 overexpression can significantly rescue the silencing effect of let-7a on MyD88 protein expression in mMCs. Mechanistically, we identified that lncRNA MEG3-205 could act as a competing endogenous RNA by binding with let-7a and thus regulate MyD88. Knockdown of lncRNA MEG3-205 alleviated albuminuria and attenuated renal inflammation and fibrosis in db/db mice. Conclusion: These findings indicated an important role of the lncRNA MEG3-205/let-7a/MyD88 axis in regulating renal inflammation and fibrosis in DN. Targeting lncRNA MEG3-205 might present a promising therapeutic strategy for DN.

Abstract Background Little is known about the association between the coexistence of diabetes mellitus (DM) and pre-existing cardiovascular disease (CVD) and mortality in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Methods A retrospective cohort study of 2939 Chinese incident CAPD patients was conducted between January 1, 2005, and December 31, 2018. The primary and secondary outcomes were all-cause and CVD mortality. The association between the coexistence of DM and pre-existing CVD and mortality was evaluated using Cox proportional hazards regression. Results Over a median of 35.1 months of follow-up, 519 patients (17.7%) died, with 258 (8.8%) being CVD-related deaths. DM plus pre-existing CVD, DM, and pre-existing CVD were associated with a higher risk of all-cause mortality (adjusted hazard ratio [HR], 2.85; 95% confidence interval [CI], 2.18 to 3.72; adjusted HR, 1.89; 95% CI, 1.50 to 2.38; and HR, 1.43; 95% CI, 1.07 to 1.92; P for tend

BackgroundIn dialysis patients, lowering low-density lipoprotein cholesterol (LDL-C) did not provide benefits, which seemed implausible in clinical practice. We hypothesized a U-shaped association between LDL-C and mortality in dialysis patients.MethodsIn this multi-center retrospective real-world cohort study, 3,565 incident Chinese peritoneal dialysis (PD) patients between January 1, 2005, and May 31, 2020, were included. The associations between baseline LDL-C and mortality were examined using cause-specific hazard models.ResultsOf 3,565 patients, 820 died, including 415 cardiovascular deaths. As compared with the reference range (2.26-2.60 mmol/L), both higher levels of LDL-C (> 2.60 mmol/L) and lower levels of LDL-C (< 2.26 mmol/L) were associated with increased risks of all-cause mortality (hazard ratio [HR],1.35, 95% confidence index [CI], 1.09-1.66; HR 1.36, 95%CI, 1.13-1.64) and cardiovascular mortality (HR, 1.31, 95% CI, 1.10-1.72; HR, 1.64; 95% CI, 1.22-2.19). Malnutrition (albumin < 36.0 g/L) modified the association between LDL-C and cardiovascular mortality (P for interaction = 0.01). A significantly increased risk of cardiovascular mortality was observed among patients with malnutrition and lower levels of LDL-C (HR 2.96, 95%CI 1.43-6.12) or higher levels of LDL-C (HR 2.81, 95%CI 1.38-5.72).ConclusionLow and high levels of LDL-C at the start of PD procedure were associated with increased all-cause and cardiovascular mortality risks. Malnutrition may modify the association of LDL-C with cardiovascular mortality.

BackgroundSerum albumin and total cholesterol are associated with mortality. In clinical practice, evaluating the association of combining album and total cholesterol with mortality may be more reasonable. Thus, we examined the association between serum albumin to total cholesterol ratio and mortality in peritoneal dialysis (PD) patients.MethodsWe conducted a retrospective cohort study of 3447 incident continuous ambulatory peritoneal dialysis (CAPD) patients from five PD centers in China from 1 January 2005 and 31 May 2020. The association between albumin to total cholesterol ratio and mortality was evaluated.ResultsWith a median follow-up of 39.3 months, 762 (22.1%) all-cause deaths occurred, including 382 (11.1%) cardiovascular deaths. As compared with a serum albumin to total cholesterol ratio of 0.77–0.82 (reference range), a higher ratio (>0.82) was associated with increased risks of all-cause mortality[hazards ratio (HR), 1.54; 95% confidence interval (CI), 1.16–2.05, E-value = 2.45] and cardiovascular mortality (HR, 2.10; 95% CI, 1.35–3.29, E-value = 3.62). A lower ratio (

BackgroundThe association between serum creatine kinase and mortality in patients with peritoneal dialysis (PD) remained unknown.MethodsWe retrospectively collected data on 3,446 incident patients with from five PD centers in China between 1 January 2005 and 31 May 2020. Creatine kinase was collected 1 week before the start of PD. We examined the association between creatine kinase and mortality using Cox proportional hazards model.ResultsThe median creatine kinase was 113 (range, 1.22–4,574) IU/L. With a median follow-up of 39.5 (range, 3.1–181.5) months, 763 (22.1%) all-cause deaths occurred, including 384 (11.1%) cardiovascular deaths. As compared with a creatine kinase of 111–179 IU/L (reference range), a higher creatine kinase (>179 IU/L) was associated with increased risks of all-cause mortality [hazards ratio (HR), 1.72; 95% CI, 1.35–2.00; E-value = 2.83] and cardiovascular mortality (HR, 1.44; 95% CI, 1.05–1.98; E-value = 2.24). As compared with the reference range, a lower creatine kinase (

Abstract Background Albumin-globulin ratio (AGR), a variable based on serum albumin and non-albumin proteins, has been demonstrated as a predictor of mortality in patients with malignant neoplasm. The aim of this study was to evaluate the prognostic value of AGR on peritoneal dialysis (PD) patients. Methods We retrospectively analyzed 602 incident PD patients from January 1st, 2008, to December 31st, 2017, at our center and followed them until December 31st, 2018. Kaplan-Meier curves and multivariate Cox regression models were applied to analyze the association between AGR and all-cause of mortality and cardiovascular mortality. Results The median follow-up time was 32.17 (interquartile range = 32.80) months. During follow-up, 131 (21.8%) patients died, including 57 patients (43.5%) who died due to cardiovascular diseases. Kaplan-Meier curves showed that patients with AGR > 1.26 had better rates of survival than those with AGR ≤ 1.25 (p

Background: Preexisting cardiovascular disease (CVD) and hypertension are each associated with poor prognosis in peritoneal dialysis (PD) patients. Joint associations of preexisting CVD and hypertension have not been comprehensively evaluated in this population. Methods: We conducted a retrospective cohort study of 3073 Chinese incident PD patients from five dialysis centres between January 1, 2005, and December 31, 2018. The joint associations between preexisting CVD, hypertension, and mortality were analysed using Cox regression models. Results: Over a median of 33.7 months of follow-up, 581 (18.6%) patients died, with 286 (9.3%) deaths due to CVD. After adjusting for confounding factors, the preexisting CVD coexisting with hypertension, preexisting CVD, and hypertension groups had higher risks of all-cause mortality (hazard ratio [HR]: 3.97, 95% confidence interval [CI]: 3.06 to 5.15; HR: 2.21, 95% CI: 1.29 to 3.79; and HR: 1.83, 95% CI: 1.47 to 2.29, respectively) and CVD mortality (HR: 4.68, 95% CI: 3.27 to 6.69; HR: 2.10, 95% CI: 0.95 to 4.62; and HR: 1.86, 95% CI: 1.36 to 2.54, respectively) than the control group without preexisting CVD or hypertension (p for trend 0.05). The joint associations showed similar patterns using the Fine–Gray competing risk models. Conclusions: Preexisting CVD and hypertension at the start of PD were additive prognostic utilities for mortality, and preexisting CVD was more strongly associated with mortality than hypertension.

Background: Lower serum chloride is associated with a higher risk of mortality in the general population. However, the association has received little attention in peritoneal dialysis patients. The study aimed to examine the association between serum chloride and mortality in peritoneal dialysis patients. Methods: In this multicenter retrospective cohort study, 2376 Chinese incident patients on peritoneal dialysis between January 1, 2005, and March 31, 2020, were included. Patients were grouped according to quartiles of serum chloride at baseline. The associations of baseline serum chloride and cardiovascular mortality and all-cause mortality were evaluated using cause-specific hazards models. Findings: Of 2376 patients, the mean age was 45.9 (45.3,46.5) years, 50.1% of patients were men. The median serum chloride levels were 103.0 (99.0,106.9) mmol/L. During 9304.5 person-years of follow-up, 462 patients died, of which 235 deaths were caused by cardiovascular disease. The highest quartile group was associated with a higher risk of cardiovascular mortality (adjusted hazards ratio [HR], 2.95; 95% confidence interval [CI], 1.80 to 4.95) and all-cause mortality (adjusted HR, 2.03; 95% CI, 1.45 to 2.83) compared with the lowest quartile. The similar trend was also found when serum chloride levels were deal as continuous variable. Interpretation: Higher serum chloride at the initial of peritoneal dialysis was associated with a higher risk of cardiovascular mortality and all-cause mortality in patients on peritoneal dialysis. Funding: This work was supported by Shanghai Municipal Health Commission (2019SY018).

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, 2.743.96. 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

Objectives. The monocyte-to-lymphocyte ratio (MLR), as a new marker of the systemic inflammatory response, is associated with cardiovascular disease (CVD) mortality in the general population and hemodialysis patients. However, the association between the MLR and CVD mortality in peritoneal dialysis (PD) has received little attention. Methods. In this multicenter retrospective cohort study, 1753 incident PD patients from November 1, 2005, to June 30, 2017, with a baseline MLR were enrolled. The primary endpoint was CVD mortality. The association of MLR with CVD mortality was assessed using a multivariable-adjusted Cox model and the Fine and Gray competing risk model. Results. Of 1753 patients, the mean age was 51.1±14.9 years, 56.9% of patients were male, and the Charlson comorbidity index was 4.29±1.75. During the follow-up period of 31.2±18.4 months, 368 patients died, of which 200 (54.3%) deaths were caused by CVD events. CVD mortality rates for the lowest, middle, and highest MLR tertiles were 70.6, 78.4, and 88.9 per 1000 patient-years, respectively (P

Chronic kidney disease is a common disease closely related to renal tubular inflammation and oxidative stress, and no effective treatment is available. Activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is an important factor in renal inflammation, but the mechanism remains unclear. Micheliolide (MCL), which is derived from parthenolide, is a new compound with antioxidative and anti-inflammatory effects and has multiple roles in tumors and inflammatory diseases. In this study, we investigated the effect of MCL on lipopolysaccharide- (LPS-) induced inflammation in renal tubular cells and the related mechanism. We found that MCL significantly suppressed the LPS-induced NF-κB signaling and inflammatory expression of cytokines, such as tumor necrosis factor-α and monocyte chemoattractant protein-1 in a rat renal proximal tubular cell line (NRK-52E). MCL also prevented LPS- and adenosine triphosphate-induced NLRP3 inflammasome activation in vitro, as evidenced by the inhibition of NLRP3 expression, caspase-1 cleavage, and interleukin-1β and interleukin-18 maturation and secretion. Additionally, MCL inhibited the reduction of mitochondrial membrane potential and decreases the release of reactive oxygen species (ROS). Moreover, MCL can prevent NLRP3 inflammasome activation induced by rotenone, a well-known mitochondrial ROS (mROS) agonist, indicating that the mechanism of MCL’s anti-inflammatory effect may be closely related to the mROS. In conclusion, our study indicates that MCL can inhibit LPS-induced renal inflammation through suppressing the mROS/NF-κB/NLRP3 axis in tubular epithelial cells.

Prior studies have shown that the levels of some platelet (PLT) indices were associated with mortality in patients undergoing hemodialysis. We aimed to investigate whether the changes in PLT indices associated with mortality in patients on peritoneal dialysis (PD). A single-center, retrospective observational cohort study was conducted in incident PD patients from 1 January 2006 to 31 December 2012, and followed up until 31 December 2014. Cox proportional hazard models were used to examine the relationships between the levels of PLT indices including PLT, plateletcrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (PLCR), and mortality. Of 1324 patients, 276 (20.8%) died during follow-up (median, 37; IQR, 3–107.4 months), among which 134 were due to cardiovascular diseases (CVD). The highest tertile of PLT levels at baseline was associated with increased risk for cardiovascular mortality after adjustment for demographic, clinical characteristics, and laboratory variables (hazard ratio [HR]:1.93; 95% confidence interval [CI]: 1.16–3.20). The similar treads were also observed in the middle and the highest tertile of the PCT level (HR: 1.68, 95%CI: 1.00–2.81 and HR: 1.89, 95%CI: 1.14–3.14, respectively). In addition, the highest tertile of PCT was associated with increased all-cause mortality (HR: 1.41, 95%CI: 1.01–1.96). However, none of the associations in MPV, PDW, and PLCR analyses reached statistical significance (HR: 0.71, 95%CI: 0.43–1.16; HR: 0.72, 95%CI: 0.45–1.18 and HR: 0.74, 95%CI: 0.46–1.19, respectively). These results suggest that higher PLT and PCT may be associated with higher risk for cardiovascular mortality in incident PD patients. Additional studies are needed to investigate whether correction of these two PLT indices reduces the risk.

BACKGROUND: Although clinical experience suggests that patients with diabetes mellitus are more susceptible to several types of infections, the overall scope of pneumonia in continuous ambulatory peritoneal dialysis (CAPD) patients with diabetic nephropathy (DN) has received little attention. METHODS: This was a prospective observational cohort study in CAPD patients in which prognostic risks of pneumonia were evaluated in DN and non-DN patients by Cox regression analysis. Hazard ratios of pneumonia events, all-cause and pneumonia-related mortality were calculated by Kaplan-Meier curves and the Cox proportional hazards model for DN versus non-DN patients. RESULTS: A total of 1148 patients (58.6% male, 48.34±15.78 years) had a median follow-up of 23.8 months and a maximum follow-up of 72.0 months. The pneumonia incidence rate of 62.3/1,000 patient-years in CAPD patients with DN was significantly higher than that of 28.5/1,000 patient-years in non-DN patients. On multivariate analysis, independent predictors of pneumonia occurrence in CAPD patients with DN were high body mass index (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.01-1.31; P = 0.037) and low serum albumin level (HR, 0.87; 95% CI, 0.78-0.98; P = 0.014). Older age (HR, 1.63; 95% CI, 1.35-1.96; P

Lung cancer is one of the most malignant diseases and a major contributor to cancer-related deaths worldwide due to the deficiency of early diagnosis and effective therapy that are of great importance for patient prognosis and quality of life. Over the past decade, the advent of clustered regularly interspaced short palindromic repeats/CRISPR associated protein (CRISPR/Cas) system has significantly propelled the progress of both fundamental research and clinical trials of lung cancer. In this review, we review the current applications of the CRISPR/Cas system in diagnosis, target identification, and treatment resistance of lung cancer. Furthermore, we summarize the development of lung cancer animal models and delivery methods based on CRISPR system, providing novel insights into clinical diagnosis and treatment strategies of lung cancer. [ABSTRACT FROM AUTHOR]