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Abstract Background Recent studies have shown that triglyceride glucose-body mass index (TyG-BMI) is associated with the risk of ischemic stroke and coronary artery disease. However, little attention has been given to the association between TyG-BMI and cardiovascular disease (CVD) mortality in patients undergoing peritoneal dialysis (PD). Therefore, this study aimed to explore the relationship between TyG-BMI and CVD mortality in southern Chinese patients undergoing PD. Methods Incident patients receiving PD from January 1, 2006, to December 31, 2018, with baseline serum triglyceride, glucose, and body mass index (BMI) information, were recruited for this single-center retrospective cohort study. TyG-BMI was calculated based on fasting plasma glucose, triglyceride, and BMI values. The association between TyG-BMI, CVD and all-cause mortality was evaluated using a multivariate-adjusted Cox proportional hazard regression model. Results Of 2,335 patients, the mean age was 46.1 ± 14.8 years; 1,382 (59.2%) were male, and 564 (24.2%) had diabetes. The median TyG-BMI was 183.7 (165.5–209.2). Multivariate linear regression showed that advanced age, male sex, history of CVD, higher levels of albumin and low-density lipoprotein cholesterol, and higher urine output were correlated with a higher TyG-BMI (P

Abstract Background Technique failure is more likely to occur during the first 12 months after peritoneal dialysis (PD) initiation, which is a great challenge encountered in PD patients. The aim of this study was to investigate the incidence and risk factors associated with technique failure within the first year of PD patients in Southern China. Methods Incident PD patients who were followed up for at least one year at The First Affiliated Hospital of Sun Yat-sen University from January 1, 2006 to December 31, 2015 were included. Technique failure was defined as transferring to hemodialysis (HD) for more than 30 days or death within the first year after start of PD. A competitive risk regression analysis was used to explore the incidence and risk factors of the technique failure. Results Overall, 2,290 incident PD patients were included in this study, with a mean age of 48.2 ± 15.7 years, 40.9% female and 25.2% with diabetes. A total of 173 patients (7.5%) had technique failure during the first year of PD. Among them, the patient death account for 62.4% (n = 108) and transferring to HD account for 37.6% (n = 65). The main reasons for death were cardiovascular diseases (n = 32, 29.6%), infection (n = 15, 13.8%) and for conversion to HD were mechanical cause (n = 28, 43.1%), infection cause (n = 22, 33.8%). The risk factors for the technique failure included advanced age (HR 2.78, 95%CI 1.82–4.30), low body mass index (BMI

Abstract Background The aims of this study were to investigate the prevalence and the influence factors of gastrointestinal symptoms, and its association with the quality of life (QOL) in peritoneal dialysis (PD) patients. Methods Continuous ambulatory PD patients (CAPD) who followed up in our PD center between March 2016 and December 2017 were enrolled in this cross-sectional study. Gastrointestinal symptom rating scale (GSRS) was used to evaluate gastrointestinal symptoms. The related clinical data were also collected. Multiple linear regression analysis was test for the influence factors associated with score of GSRS and QOL. Results This study included 471 CAPD patients. The mean age was 48.5±13.9 years, 53.9% were male and 15.1% with diabetic nephropathy. The median duration of PD was 37.3 (17.5~66.5) months. The median score of GSRS was 1.2(1.1~1.3) scores. Totally 82.2% (n=387) CAPD patients had at least one gastrointestinal symptom. Higher glycosylated hemoglobin, higher score of depression, lower diastolic blood pressure, urine output, score of instrumental activities of daily living scale and more amount of pills per day were independently associated with higher score of GSRS (all P

Abstract Background The receptor-binding domain (RBD) variants of SARS-CoV-2 could impair antibody-mediated neutralization of the virus by host immunity; thus, prospective surveillance of antibody escape mutants and understanding the evolution of RBD are urgently needed. Methods Using the single B cell cloning technology, we isolated and characterized 93 RBD-specific antibodies from the memory B cells of four COVID-19 convalescent individuals in the early stage of the pandemic. Then, global RBD alanine scanning with a panel of 19 selected neutralizing antibodies (NAbs), including several broadly reactive NAbs, was performed. Furthermore, we assessed the impact of single natural mutation or co-mutations of concern at key positions of RBD on the neutralization escape and ACE2 binding function by recombinant proteins and pseudoviruses. Results Thirty-three amino acid positions within four independent antigenic sites (1 to 4) of RBD were identified as valuable indicators of antigenic changes in the RBD. The comprehensive escape mutation map not only confirms the widely circulating strains carrying important immune escape RBD mutations such as K417N, E484K, and L452R, but also facilitates the discovery of new immune escape-enabling mutations such as F486L, N450K, F490S, and R346S. Of note, these escape mutations could not affect the ACE2 binding affinity of RBD, among which L452R even enhanced binding. Furthermore, we showed that RBD co-mutations K417N, E484K, and N501Y present in B.1.351 appear more resistant to NAbs and human convalescent plasma from the early stage of the pandemic, possibly due to an additive effect. Conversely, double mutations E484Q and L452R present in B.1.617.1 variant show partial antibody evasion with no evidence for an additive effect. Conclusions Our study provides a global view of the determinants for neutralizing antibody recognition, antigenic conservation, and RBD conformation. The in-depth escape maps may have value for prospective surveillance of SARS-CoV-2 immune escape variants. Special attention should be paid to the accumulation of co-mutations at distinct major antigenic sites. Finally, the new broadly reactive NAbs described here represent new potential opportunities for the prevention and treatment of COVID-19.

Abstract Background Rehospitalization is a major problem for end stage renal disease (ESRD) populations. However, researches on 30-day unexpected rehospitalzation of incident peritoneal dialysis (PD) patients were limited. This study aimed to investigate the prevalence, risk factors and impact on outcomes of 30-day unexpected rehospitalization in incident PD patients. Methods This was a retrospective cohort study. Patients who accepted PD catheter implantation in our centre from Jan 1, 2006 to Dec 31, 2013 and regular follow-up were included. The demographic characteristics, laboratory parameters, and rehospitalization data were collected and analyzed. The primary outcome was all-cause mortality, and the secondary outcomes included cardiovascular disease (CVD) mortality and technical failure. Results Totally 1632 patients (46.9 ± 15.3 years old, 60.1% male, 25.6% with diabetes) were included. Among them, 149 (9.1%) had a 30-day unexpected rehospitalization after discharge. PD-related peritonitis (n = 48, 32.2%), catheter malfunction (n = 30, 20.1%) and severe fluid overload (n = 19, 12.8%) were the top three causes for the rehospitalization. Multivariate logistic regression analysis showed that length of index hospital stays [Odds ratio (OR) =1.02, 95% confidence interval (CI) 1.00–1.03, P = 0.036) and hyponatremia (OR = 1.85, 95% CI 1.06–3.24, P = 0.031) were independently associated with the rehospitalization. Multivariate Cox regression analysis indicated that 30-day rehospitalization was an independent risk factor for all-cause mortality [Hazard ratio (HR) =1.52, 95% CI 1.07–2.16, P = 0.019) and CVD mortality (HR = 1.73, 95% CI 1.03–2.90, P = 0.038). Conclusions The prevalence of 30-day unexpected rehospitalization for incident PD patients in our centre was 9.1%. The top three causes for the rehospitalization were PD-related peritonitis, catheter malfunction and severe fluid overload. Thirty-day unexpected rehospitalization increased the risk of all-cause mortality and CVD mortality for PD patients.

Abstract Background There have been few systematic studies regarding clearance of uric acid (UA) in patients undergoing peritoneal dialysis (PD). This study investigated peritoneal UA removal and its influencing factors in patients undergoing PD. Methods This cross-sectional study enrolled patients who underwent peritoneal equilibration test and assessment of Kt/V from April 1, 2018 to August 31, 2019. Demographic data and clinical and laboratory parameters were collected, including UA levels in dialysate, blood, and urine. Results In total, 180 prevalent patients undergoing PD (52.8% men) were included. Compared with the normal serum UA (SUA) group, the hyperuricemia group showed significantly lower peritoneal UA clearance (39.1 ± 6.2 vs. 42.0 ± 8.0 L/week/1.73m2; P = 0.008). Furthermore, higher transporters (high or high-average) exhibited greater peritoneal UA clearance, compared with lower transporters (low or low-average) (42.0 ± 7.0 vs. 36.4 ± 5.6 L/week/1.73 m2; P 39.8 L/week/1.73m2). Conclusions For patients undergoing PD who exhibited worse residual kidney function, peritoneal clearance dominated in SUA balance. Increasing dialysis dose or average glucose concentration may aid in controlling hyperuricemia in lower transporters.

Abstract Background The low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio constitutes a strong risk predictor of cardiovascular events. However, the association between this ratio and cardiovascular death in peritoneal dialysis (PD) patients is uncertain. The study aimed to investigate whether a high LDL-C/HDL-C ratio could predict both cardiovascular and all-cause mortalities in patients on PD. Methods A total of 1616 incident patients on PD included from January 1, 2006 to December 31, 2013 were followed up with until 31 December 2018 in this single-center prospective cohort study. Participants were divided into three categories according to LDL-C/HDL-C ratio tertile. The primary endpoint was cardiovascular mortality; the secondary endpoint was all-cause mortality. Results The mean age of the study cohort was 47.5 years and the mean body mass index (BMI) was 21.6 kg/m2. During a median follow-up period of 47.6 months, 492 patients died, including 246 (50.0%) due to cardiovascular disease (CVD). A multivariate analysis revealed that the highest LDL-C/HDL-C ratio tertile was significantly associated with increased CVD mortality [hazard ratio (HR): 1.69, 95% CI: 1.24–2.29; P = 0.001] and all-cause mortality (HR: 1.46, 95% CI: 1.18–1.81; P = 0.001) relative to the lowest tertile. After adjusting for covariates, the HRs of cardiovascular and all-cause mortalities were 1.84 (95% CI: 1.25–2.71; P = 0.002) and 1.35 (95% CI: 1.03–1.77; P = 0.032). Subgroup analysis showed that the risk of CVD death rose with a higher LDL-C/HDL-C ratio among PD patients who were female, younger than 65 years old, without being malnourished (BMI ≥ 18.5 kg/m2 or albumin ≥35 g/L), and with a history of diabetes or CVD, respectively. Conclusions A high LDL-C/HDL-C ratio is an independent risk factor for both cardiovascular and all-cause mortalities among PD patients.

Abstract Background Urgent-start peritoneal dialysis (PD) can help patients with end-stage renal diseases (ESRD) that are referred late to dialysis. However, catheter patency and related complications of urgent-start PD have not been thoroughly clarified. We investigated the clinical outcomes of urgent-start PD in a Chinese cohort. Methods We enrolled ESRD patients who received urgent-start PD (starting PD within 14 days after catheter insertion) in our center from January 1, 2006 to December 31, 2014, and followed them up for 10 years. The primary outcome was catheter failure. Secondary outcomes included short-term and long-term complications related to urgent-start PD. Results Totally 2059 patients (58.9% male, mean age 47.6 ± 15.9 years) were enrolled. Few perioperative complications were observed, including significant hemorrhage (n = 3, 0.1%) and bowel perforation (n = 0). Early peritonitis occurred in 24 (1.2%) patients (0.28 episodes per patient-year). Within the first month after catheter insertion, functional catheter malfunction occurred in 85 (4.1%) patients, and abdominal wall complications (including hernia, hydrothorax, hydrocele, and leakage) in 36 (1.7%) patients. During a median 36.5 (17.7–61.4) months of follow-up, 75 (3.6%) patients experienced catheter failure, and 291 (14.1%) had death-censoring technique failure. At the end of 1-month, 1 -year, 3-year, and 5-year, catheter patency rate was 97.6, 96.4, 96.2, 96.2%; and technique survival rate was 99.5, 97.0, 90.3, 82.7%, respectively. After adjusting for confounders, every 5-year increase in age was associated with 19% decrease of risk for catheter failure (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.73–0.89). Male sex (HR: 1.43, 95% CI: 1.00–2.04), diabetic nephropathy (HR: 1.56, 95% CI: 1.08–2.25) and low hemoglobin levels (HR: 0.89, 95% CI: 0.81–0.98) were independent risk factors for abdominal wall complications. Conclusions Urgent-start PD is a safe and efficacious option for unplanned ESRD patients. A well-trained PD team, a standardized catheter insertion procedure by experienced nephrologists, and a carefully designed initial PD prescription as well as comprehensive follow-up care, might be essential for the successful urgent-start PD program.

Abstract Background Inflammation-based prognostic scores have been used as outcome predictors in patients with cancer or on hemodialysis. However, their role in patients on continuous ambulatory peritoneal dialysis (CAPD) remains unclear. This study aimed to examine the prognostic value of inflammation-based composite scores for mortality in CAPD patients. Methods This study was conducted in CAPD patients enrolled from January 1, 2006 to December 31, 2014 and followed until December 31, 2016. Three inflammation-based prognostic scores, including Glasgow prognostic score (GPS), prognostic nutritional index (PNI), and prognostic index (PI), were conducted in this study. The associations between these scores and all-cause or cardiovascular mortality were evaluated by Kaplan–Meier method and Cox proportional hazards models. The areas under the curve (AUC) of receiver-operating characteristic (ROC) analysis were used to determine the predictive values of mortality. Results A total of 1501 patients were included. During a median follow-up of 38.7 (range, 21.6–62.3) months, 346 (23.1%) patients died, of which 168 (48.6%) were due to cardiovascular diseases (CVD). After adjustment for confounders, the results showed that elevated GPS, PNI, and PI scores were all independently associated with all-cause [GPS: Score 1: hazard ratio(HR) 3.94, 95% confidence interval(CI) 2.90–5.35; Score 2: HR 7.56, 95% CI 5.35–10.67; PNI: HR 1.82, 95% CI 1.36–2.43; PI: Score 1: HR 2.08, 95% CI 1.63–2.65; Score 2: HR 3.03, 95% CI 2.00–4.60)] and CVD mortality(GPS: Score 1: HR 4.41, 95% CI 2.76–7.03; Score 2: HR 9.64, 95% CI 5.72–16.26; PNI: HR 1.63, 95% CI 1.06–2.51; PI: Score 1: HR 2.57, 95% CI 1.81–3.66, Score 2: HR 3.85, 95% CI 1.99–7.46).The AUC values of GPS score were 0.798 (95% CI0.770–0.826) for all-cause mortality and 0.781 (95% CI 0.744–0.817) for CVD mortality, both of which significantly higher than those of PNI and PI scores (P

Abstract Introduction Stromal cell-derived factor-1 (SDF-1) is a newly discovered small molecule adipocytokine, and research has shown that it is closely related to the occurrence and development of obesity. However, there are currently few research reports on SDF-1 in childhood obesity and nonalcoholic fatty liver disease (NAFLD), and this study aims to explore the relationship between SDF-1 and obesity related indicators in obese children. Methods Serum SDF-1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Clinical and biochemical data were collected, such as body mass index (BMI), waist and hip circumference, blood pressure, liver enzymes, cholesterol, and fasting insulin. Children with NAFLD or not were evaluated through Color Doppler Ultrasound. Results Serum SDF-1 concentrations were significantly higher in obese subjects than in non-obese subjects (P

Abstract Aim Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood, with genetic susceptibility and pathological processes such as autoimmunity and autoinflammation, but its pathogenesis is unclear. We conducted a transcriptome-wide association study (TWAS) using expression interpolation from a large-scale genome-wide association study (GWAS) dataset to identify genes, biological pathways, and environmental chemicals associated with JIA. Methods We obtained published GWAS data on JIA for TWAS and used mRNA expression profiling to validate the genes identified by TWAS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. A protein–protein interaction (PPI) network was generated, and central genes were obtained using Molecular Complex Detection (MCODE). Finally, chemical gene expression datasets were obtained from the Comparative Toxicogenomics database for chemical genome enrichment analysis. Results TWAS identified 1481 genes associated with JIA, and 154 differentially expressed genes were identified based on mRNA expression profiles. After comparing the results of TWAS and mRNA expression profiles, we obtained eight overlapping genes. GO and KEGG enrichment analyses of the genes identified by TWAS yielded 163 pathways, and PPI network analysis as well as MCODE resolution identified a total of eight clusters. Through chemical gene set enrichment analysis, 287 environmental chemicals associated with JIA were identified. Conclusion By integrating TWAS and mRNA expression profiles, genes, biological pathways, and environmental chemicals associated with JIA were identified. Our findings provide new insights into the pathogenesis of JIA, including candidate genetic and environmental factors contributing to its onset and progression.

Abstract Background We measured the concentrations of the adipocytokines vaspin and visfatin in obese Chinese children. Furthermore, we studied the correlation of these adipocytokines with early-onset metabolic and vascular sequelae among these children. Methods A total of 244 children (160 obese and 84 lean) were included in this study. Vaspin and visfatin were detected using enzyme-linked immunosorbent assays. We also assayed other metabolic and cardiovascular parameters. The associations of serum vaspin and visfatin concentrations with metabolic and cardiovascular parameters were determined. Results We found a significant elevation in the concentrations of vaspin and visfatin in obese children compared to the concentrations in lean children. Additionally, we found a significant positive correlation between visfatin and vaspin levels, as well as inflammatory cell infiltration and markers of endothelial activation, but these factors did not affect insulin resistance in obese children. Multiple regression analyses confirmed that vaspin is the strongest predictor of higher tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), angiotensin-2 (Ang-2), vascular cellular adhesion molecule-1 (VCAM-1), and E-selectin levels. We also found a significant association between visfatin and Ang-2, IL-6, VCAM-1, and E-selectin levels. Conclusion The adipocytokines vaspin and visfatin are significantly interrelated, and both adipocytokines play a role in vascular endothelial function and inflammation.

Abstract Background The prevalence of childhood obesity and obesity-related metabolic disorder such as dyslipidemia has sharply increased in the past few decades. Chronic low-grade inflammation is associated with the development of comorbidities and poor prognosis in obesity. This study aims to evaluate interleukin-10 (IL-10) in childhood obesity with hypertriglyceridemia. Method We evaluated IL-10 and signal transducer and activator of transcription 3 (STAT3) mRNA expression in adipose tissue (AT) as well as serum IL-10 in 62 children of 3 groups and in high-fat diet (HFD) induced obese rat. Expression of IL-10 and STAT3 protein in AT of diet-induced obese rats were examined over feed period. Results Adipose IL-10 and STAT3 mRNA expression and serum IL-10 reduced in obese children with hypertriglyceridemia and in HFD obese rats. The protein expression of IL-10 and STAT3 decreased in AT of obese rats compared with the control rats at end time. Expression of IL-10 mRNA was negatively correlated to TG and LDL-C levels, and positively correlated to HDL-C, adiponectin and serum IL-10 levels. Conclusions IL-10 expression and its downstream JAK-STAT pathway are down-regulated in obese children with hypertriglyceridemia and in HFD obese rats.