Background:The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and prognosis in patients with end-stage renal disease (ESRD) remains controversial. The aim of this study is to explore the association of NHHR with cardiovascular disease (CVD) mortality as well as all-cause mortality in peritoneal dialysis (PD) patients. Methods:In this single-center prospective observational cohort study, 1,616 individuals undergoing PD were recruited with a median follow-up duration of 47.6 months. The association of NHHR with overall CVD mortality, as well as atherosclerotic and non-atherosclerotic subtypes, was assessed using competing risk regression models. Additionally, multivariable Cox proportional hazards regression was employed to evaluate the relationship between NHHR and all-cause mortality. Critical baseline covariates were adjusted in these multivariable models. Results:In the end, 552 patients (34.2%) died, of whom 264 (47.8%) died from CVD mortality, corresponding to incidence rates of 71.18 and 34.04 per 1,000 person-years, respectively. In multivariable analyses, competing risk regression model showed no significant association between NHHR and overall CVD mortality. However, each 1- standard deviation (SD) increase in NHHR level was associated with a 35% higher risk of atherosclerotic CVD mortality (sub-distribution hazard ratio [SHR] 1.35, 95% Confidence interval [CI] 1.17-1.56), and a 27% lower risk of non-atherosclerotic CVD mortality (SHR 0.73, 95% CI 0.58-0.93), respectively. Cox regression model indicated that each 1-SD increase in NHHR level was independently associated with a 16% increase in all-cause mortality (HR 1.16, 95% CI 1.06-1.26). Quartile-based analysis reinforced these findings. Conclusion:An elevated NHHR level conferred an increased risk of atherosclerotic CVD and all-cause mortality, yet showed a paradoxical association with reduced non-atherosclerotic CVD mortality in PD patients.

Background and objective:Assessing the impact of chemotherapy-induced nausea and vomiting (CINV) on the quality of life (QoL) of cancer patients is critical. However, there is a dearth of specialized assessment tools designed specifically for pediatric cancer patients. The aim of this study was to develop and validate the Pediatrics Functional Living Index-Emesis (PFLIE) as a patient-reported outcome measure (PROM) to assess the impact of CINV on QoL in pediatric patients. This study was approved by the Institutional Review Board of Sun Yat-sen University Cancer Center (Approval No. B2021-113-01) and was conducted in accordance with the Declaration of Helsinki.​. Materials and methods:The reliability, content validity, structural validity, and concurrent validity of the PFLIE were assessed through two rounds of Delphi expert consultation and a questionnaire survey of 90 pediatric cancer patients receiving chemotherapy at a tertiary care hospital cancer center in China. Results:The PFLIE consists of two domains: nausea (10 items) and vomiting (10 items). The content validity index (CVI) for both the nausea and vomiting domains was 0.933. The Cronbach's alpha coefficients for the total scale, nausea domain, and vomiting domain were 0.964, 0.928, and 0.943, respectively. Item-domain correlations were stronger for the PFLIE (r = 0.678-0.882) across domains compared to across-domain correlations (r = 0.493-0.780), suggesting that the PFLIE has acceptable construct validity. In addition, the PFLIE demonstrated acceptable concurrent validity. Conclusions:The validity and reliability of the Chinese version of the PFLIE are reliable and valid. The tool can help healthcare providers effectively identify and manage CINV symptoms, thereby improving the QoL of pediatric cancer patients. In low- and middle-income countries (LMICs) with limited resources, PFLIE can be used to improve the management of CINV and to ensure that pediatric cancer patients receive adequate care despite inadequate healthcare infrastructures. The tool can be used to improve the management of CINV and to ensure that pediatric cancer patients receive adequate care despite inadequate healthcare infrastructures.​.

Introduction: Platelets play parts in infection and immune processes. However, the association between platelet count and the risk of peritoneal dialysis (PD)-associated peritonitis is unclear. Methods: This was a retrospective, observational, single-center cohort study. A Cox regression analysis was used to evaluate the independent association of platelet count with the occurrence of first PD-associated peritonitis. Models were adjusted for gender, age, body mass index, cardiovascular disease, diabetes mellitus, white blood cell count, neutrophil-lymphocyte ratio, hemoglobin level, albumin level, potassium level, and anti-platelet medication usage. Results: A total of 2,374 patients were enrolled in this study (59% men; mean age 47.40 +/- 12.12). The average platelet count was 229.30 +/- 82.12 x 10(9)/L. 467 (20%) patients suffered from PD-associated peritonitis at least once. In the multivariable model, the adjusted hazard ratios (HRs) for quartiles 2, 3 and 4 versus quartile 1 were 1.428 (95% CI 1.060-1.924, p = 0.019), 1.663 (95% CI 1.240-2.229, p < 0.001) and 1.843 (95% CI 1.363-2.492, p < 0.001) with baseline data. A nonlinear relationship between platelet count and first PD-associated peritonitis was observed. Further, the association between platelet and first PD-associated peritonitis was significant in the patients with hypokalemia (P for interaction = 0.040). Conclusion: In PD patients, elevated platelet counts were significantly associated with an increased risk of the first onset of PD-associated peritonitis.

Kidney fibrosis is a common fate of chronic kidney diseases (CKDs), eventually leading to renal dysfunction. Yet, no effective treatment for this pathological process has been achieved. During the bioassay-guided chemical investigation of the medicinal plant Wikstroemia chamaedaphne, a daphne diterpenoid, daphnepedunin A (DA), is characterized as a promising anti-renal fibrotic lead. DA shows significant anti-kidney fibrosis effects in cultured renal fibroblasts and unilateral ureteral obstructed mice, being more potent than the clinical trial drug pirfenidone. Leveraging the thermal proteome profiling strategy, cell division cycle 42 (Cdc42) is identified as the direct target of DA. Mechanistically, DA targets to reduce Cdc42 activity and down-regulates its downstream phospho-protein kinase Cζ(p-PKCζ)/phospho-glycogen synthase kinase-3β (p-GSK-3β), thereby promoting β-catenin Ser33/37/Thr41 phosphorylation and ubiquitin-dependent proteolysis to block classical pro-fibrotic β-catenin signaling. These findings suggest that Cdc42 is a promising therapeutic target for kidney fibrosis, and highlight DA as a potent Cdc42 inhibitor for combating CKDs.

Purpose: The prognosis of patients receiving peritoneal dialysis (PD) is associated with inflammation. Systemic immune-inflammation index (SII) is one of inflammatory markers, and the role in predicting clinical outcomes in PD patients is unclear. We aimed to investigate the relationship between the SII and all-cause and cardiovascular-specific mortalities in patients undergoing PD.Patients and Methods: A total of 1419 PD patients from the First Affiliated Hospital of Sun Yat-sen University between January 1, 2007 and December 31, 2019 were retrospectively included at baseline, and the patients were followed up until November 31, 2021. SII was calculated as platelet countxneutrophil count/lymphocyte count. Kaplan-Meier curves and Cox proportional hazards regression models were used to determine the relationship between SII levels and all-cause and cardiovascular-specific mortalities.Results: During follow-up (median period was 42 months), 321 patients died (171 died of cardiovascular disease). With adjustment for the potential confounding factors, each 1-SD increase in the SII was associated with 20.2% increase in all-cause mortality (hazard ratio [HR]: 1.202, 95% confidence interval [CI]: 1.088-1.327, P<0.001) and 28.0% increase in cardiovascular-specific mortality (HR: 1.280, 95% CI: 1.126-1.456, P<0.001). High SII (vs low SII) was significantly associated with increased risks of all-cause mortality (HR: 1.391, 95% CI: 1.066-1.815, P-value: 0.015) and cardiovascular-specific mortality (HR: 1.637, 95% CI: 1.185-2.261, P-value: 0.003). Subgroups analyses showed similar results for those younger than 65-year-old only.Conclusion: Elevated SII level was independently associated with increased risks of all-cause and cardiovascular-specific mortalities in PD patients, especially for those younger than 65-year-old.

Dietary iron intake is closely related to the incidence of colorectal cancer. However, the interactions among dietary iron, gut microbiota, and epithelial cells in promoting tumorigenesis have rarely been discussed. Here, we report that gut microbiota plays a crucial role in promoting colorectal tumorigenesis in multiple mice models under excessive dietary iron intake. Gut microbiota modulated by excessive dietary iron are pathogenic, irritating the permeability of the gut barrier and causing leakage of lumen bacteria. Mechanistically, epithelial cells released more secretory leukocyte protease inhibitor (SLPI) to combat the leaked bacteria and limit inflammation. The upregulated SLPI acted as a pro-tumorigenic factor and promoted colorectal tumorigenesis by activating the MAPK signaling pathway. Moreover, excessive dietary iron significantly depleted Akkermansiaceae in the gut microbiota; while supplementation with Akkermansia muciniphila could successfully attenuate the tumorigenic effect from excessive dietary iron. Overall, excessive dietary iron perturbs diet - microbiome-epithelium interactions, which contributes to intestinal tumor initiation.

Mesenteric adipose tissue (MAT) in Crohn's disease (CD) is associated with transmural inflammation. Extended mesenteric excision can reduce surgical recurrence and improve long‐term outcomes, indicating that MAT plays an important role in the pathogenesis of CD. Bacterial translocation has been reported to occur in the MAT of patients with CD (CD‐MAT), but the mechanisms by which translocated bacteria lead to intestinal colitis remain unclear. Here it is shown that members of Enterobacteriaceae are highly enriched in CD‐MAT compared with non‐CD controls. Viable Klebsiella variicola in Enterobacteriaceae is isolated exclusively in CD‐MAT and can induce a pro‐inflammatory response in vitro and exacerbates colitis both in dextran sulfate sodium (DSS)‐induced colitis mice model and IL‐10 −/− spontaneous colitis mice model. Mechanistically, active type VI secretion system (T6SS) is identified in the genome of K. variicola , which can impair the intestinal barrier by inhibiting the zonula occludens (ZO‐1) expression. Dysfunction of T6SS by CRISPR interference system alleviates the inhibitory effect of K. variicola on ZO‐1 expression and attenuated colitis in mice. Overall, these findings demonstrate that a novel colitis‐promoting bacteria exist in the mesenteric adipose tissue of CD, opening a new therapeutic avenue for colitis management.

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.

BackgroundAlthough the ratio of apolipoprotein B (apo B) to apolipoprotein A1 (apo A1) (apo B/apo A1) seems to be associated with mortality in hemodialysis (HD) patients, the association of apo B/apo A1 ratio with death remains not clear in peritoneal dialysis (PD) patients.AimsThe study targets to examine the relationship of apo B/apo A1 ratio with survival in patients receiving PD treatment.MethodsIn this single-center prospective observational cohort study, we enrolled 1,616 patients receiving PD treatment with a median follow-up time of 47.6 months. We used a multivariable Cox proportional hazards model to examine the relationship between apo B/apo A1 ratio and cardiovascular (CV) and all-cause mortality. The association of apo B/apo A1 ratio with atherosclerotic and non-atherosclerotic CV mortality was further evaluated by competing risk regression models.ResultsDuring the follow-up, 508 (31.4%) patients died, 249 (49.0%) died from CV events, of which 149 (59.8%) were atherosclerotic CV mortality. In multivariable models, for 1-SD increase in apo B/apo A1 ratio level, the adjusted hazard ratios for CV and all-cause mortality were 1.26 [95% confidence interval (CI), 1.07–1.47; P = 0.005] and 1.20 (95% CI, 1.07–1.35; P = 0.003), respectively. The adjusted subdistribution hazard ratios for atherosclerotic and non-atherosclerotic CV mortality were 1.43 (95% CI, 1.19–1.73; P < 0.001) and 0.85 (95% CI, 0.64–1.13; P = 0.256), respectively. For quartile analysis, patients in quartile 4 had higher CV, all-cause, and atherosclerotic CV mortality compared with those in quartile 1. Moreover, apo B/apo A1 ratio had a diabetes-related difference in CV, all-cause, and atherosclerotic CV mortality.ConclusionElevated apo B/apo A1 ratio level was significantly associated with CV, all-cause, and atherosclerotic CV mortality in patients undergoing PD. Moreover, the association was especially statistically significant in patients with diabetes.

Background: The association between non-high-density lipoprotein cholesterol (non-HDL-C) and mortality in patients undergoing peritoneal dialysis (PD) is unclear. Objective: The aim of this study was to evaluate the association of non-HDL-C with cardiovascular (CV) and all-cause mortality in PD patients. Methods: We conducted a prospective cohort study. A total of 1,616 incident PD patients from a single PD center in South China were followed for a median of 47.6 months. The independent association of non-HDL-C with CV and all-cause mortality was evaluated by a Cox regression analysis. Results: During the follow-up period, 508 (31.4%) patients died, of which 249 (49.0%) were due to CV events. Atherosclerotic CV mortality accounted for 59.8% of CV mortality. In multivariable models, for 1-SD increase in non-HDL-C level, the hazard ratios (HRs) for CV and all-cause mortality were 1.52 [95% confidence interval (CI), 1.32-1.75; P < 0.001)] and 1.24 (95% CI, 1.12-1.39; P < 0.001), respectively. Furthermore, non-HDL-C was positively associated with atherosclerotic CV mortality (HR, 1.29; 95% CI, 1.09-1.52; P = 0.004) but not associated with nonatherosclerotic CV mortality (HR, 0.79; 95% CI, 0.59-1.05; P = 0.108). The quartile analyses showed a similar pattern to the continuous variable analyses of non-HDL-C levels for CV and all-cause mortality but did not demonstrate statistical significance for atherosclerotic or nonatherosclerotic CV mortality. Conclusion: An elevated non-HDL-C level was independently associated with an increased risk of CV mortality, especially atherosclerotic CV mortality, and all-cause mortality in incident PD patients. (C) 2021 National Lipid Association. Published by Elsevier Inc. All rights reserved.

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 Plasma fibrinogen is significantly associated with cardiovascular (CV) events and mortality in the general population. However, the association between plasma fibrinogen and mortality in patients undergoing peritoneal dialysis (PD) is unclear. Methods This was a prospective cohort study. A total of 1603 incident PD patients from a single center in South China were followed for a median of 46.7 months. A Cox regression analysis was used to evaluate the independent association of plasma fibrinogen with CV and all-cause mortality. Models were adjusted for age, sex, smoking, a history of CV events, diabetes, body mass index, systolic blood pressure, hemoglobin, blood platelet count, serum potassium, serum albumin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, hypersensitive C-reactive protein, estimated glomerular filtration rate, antiplatelet agents and lipid-lowering drugs. Results The mean age was 47.4 ± 15.3 years, 955 (59.6%) patients were male, 319 (19.9%) had a history of CV events, and 410 (25.6%) had diabetes. The average plasma fibrinogen level was 4.12 ± 1.38 g/L. Of the 474 (29.6%) patients who died during follow-up, 235 (49.6%) died due to CV events. In multivariable models, the adjusted hazard ratios (HRs) for quartile 1, quartile 3, and quartile 4 versus quartile 2 were 1.18 (95% confidence interval [CI], 0.72–1.95, P = 0.51), 1.47 (95% CI, 0.93–2.33, P = 0.10), and 1.78 (95% CI, 1.15–2.77, P = 0.01) for CV mortality and 1.20 (95% CI, 0.86–1.68, P = 0.28), 1.29 (95% CI, 0.93–1.78, P = 0.13), and 1.53 (95% CI, 1.12–2.09, P = 0.007) for all-cause mortality, respectively. A nonlinear relationship between plasma fibrinogen and CV and all-cause mortality was observed. Conclusions An elevated plasma fibrinogen level was significantly associated with an increased risk of CV and all-cause mortality in patients undergoing PD.

BACKGROUND High incidence of sports injury occurring during marathon competitions urges a pressing demand for a convenient and accurate diagnostic tool of such injuries. However, contemporary information on the application of Musculoskeletal Ultrasonography (MSUS) in sports injury is not sufficient. METHODS A repeated measures study was used to describe the distribution of lower limb injuries in the Chongqing marathon and the application of MSUS in assessing these sports injuries. To verify the diagnostic accuracy of MSUS for sports injury, participants were assigned to group A (MSUS group) or group B (Sports medicine physician, ie SMP group), each group had an independent procedure of making a diagnosis. That is, ultrasound physicians in group A made a diagnosis from the ultrasonographic images while sports medicine physicians in group B synthesizing symptoms and signs of patients to identify the exact injury. RESULTS No statistically significant difference was found in the participants of the baseline characteristics between the two groups (p > 0.05). In both groups, the knee was accounted as the vast majority of running injury sites, followed by the ankle (p = 0.152). Tendons and ligaments injuries (x2 = 48.437 and p = 0.000) were the most common types of injury. Visual analog scale (VAS), a higher score of which indicates severer pain (0 to 10), was used to evaluate the severity of pain from injuries. VAS scores decreased significantly (p < 0.05) in both groups after immediate treatment and the decrease in Group A was significantly greater than Group B (p = 0.007). For athletes with pain sustained or exacerbated, further MRI exam showed a concordance rate of approximately 100% between MSUS and MRI diagnosis. CONCLUSIONS Musculoskeletal ultrasonography could be applied as an efficient method for the diagnosis of sports injuries in the athletic competition field.

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.