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Purpose: This study assessed the effect of amoxicillin on outcomes in intensive care unit (ICU) patients with acute kidney injury (AKI), focusing on mortality rates and acute kidney disease (AKD) occurrence., Materials and Methods: We conducted a retrospective cohort analysis utilizing data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The study included intensive care unit patients diagnosed with AKI to assess the effects of post-admission amoxicillin administration on 30-day and 90-day mortality rates and acute kidney disease incidence. We employed Cox proportional hazards models, propensity score matching, and inverse probability of treatment weighting to control for potential confounders., Results: Among 24,650 AKI patients, 676 (2.7%) received amoxicillin. The results indicated significantly lower mortality rates at 30 days (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.42-0.69) and 90 days (HR 0.64, 95% CI 0.52-0.77) in the amoxicillin group compared to non-recipients. Additionally, amoxicillin administration was associated with a reduced incidence of AKD (HR 0.49, 95% CI 0.36-0.65) but resulted in a modestly increased length of hospital stay (mean difference [MD] 1.95 days, 95% CI 1.15-2.75). A dose‒response relationship was evident, with higher doses (>875 mg) further decreasing mortality rates. Subgroup analysis revealed consistent benefits across most patient groups., Conclusion: Amoxicillin administration following ICU admission in patients with AKI was associated with improved survival rates and a lower incidence of AKD, highlighting its potential as a therapeutic measure for AKI management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Luo, Zhou, Wan, Peng, Liao and Su.)

Kidney diseases are major global health problems, with high prevalence and mortality. However, current treatment strategies for kidney diseases fail to achieve satisfactory efficacy. Mesenchymal stem cell (MSC)-based therapy has been a promising strategy for treating kidney diseases. Preclinical studies have proven their safety and effectiveness in treating acute kidney injury (AKI) and chronic kidney disease (CKD), but the outcomes of clinical trials have shown very limited clinical efficacy. A variety of innovative approaches have been proposed to enhance the therapeutic potential of MSCs, and hydrogels are attractive candidates. Hydrogels are three-dimensional (3D) networks formed by hydrophilic polymers of natural or synthetic origin with diverse physical and chemical properties. They have been widely applied in the field of drug delivery and regenerative medicine, including MSC-based therapy. Many studies have proven that hydrogels can improve the therapeutic efficacy of MSCs for kidney diseases, but there are still challenges limiting the widespread application of this method. In this review, we introduce the application of MSCs in kidney diseases and the factors that influence therapeutic efficiency and focus on the beneficial effects of hydrogels in MSC-based therapy for AKI and CKD.

Background: The incidence of pruritus associated with hemodialysis (HD) patients can be as high as 70%, and ~ 40% of patients suffer from moderate to severe systemic pruritus. Difelikefalin (CR845), a peripheral restrictor κ-opioid receptor agonist, activates opioid receptors on peripheral neurons and immune cells to relieve pruritus in patients. However, the clinical effect of difelikefalin on HD-related pruritus is unclear. Therefore, the purpose of this meta-analysis and systematic review was to investigate the safety and efficacy of difelikefalin in the treatment of HD-associated pruritus., Objective: This study explored the efficacy and safety of difelikefalin in the treatment of pruritus in HD patients by systematic review and meta-analysis., Materials and Methods: Randomized controlled trials on difelikefalin in the treatment of pruritus in HD patients were retrieved from PubMed, Embase, Cochrane Library, and Web of Science electronic databases. The retrieval deadline was January 1, 2023. Stata 15.0 software was used for data analysis of the included studies., Results: A total of 4 randomized controlled trials were included, totaling 1,268 patients (736 patients in the experimental group and 532 patients in the control group). Results of the meta-analysis showed that, compared with the control group, difelikefalin could significantly improve the Worst Itch Numeric Rating Scale score (improvement > 3; risk ratio (RR) = 1.28, 95% confidence interval (CI) (1.07, 1.53)), decrease the 5-D itch score (standardized mean difference = -0.43, 95% CI (-0.55, -0.30)), and significantly improve adverse events (RR = 1.33, 95% CI (1.13, 1.56))., Conclusion: Although difelikefalin can improve itching symptoms in HD patients, it can also increase adverse reactions based on the current literature. Therefore, more studies are needed to further explore the safety and efficacy of difelikefalin treatment.

Controversial data have been reported on the prognostic value of C-X-C motif chemokine receptor 4 (CXCR4) in chronic lymphocytic leukemia (CLL). This prospective, single-center, observational study aimed to evaluate the role of CXCR4 in the pathophysiology of CLL and its prognostic role. A total of 158 patients of CLL were enrolled, and CXCR4 expression on CLL cells was detected by flow cytometry (FCM) at initial diagnosis. The patients were divided into 2 groups according to the CXCR4 mean fluorescence intensity (MFI) median. Also, four patient specimens from the CXCR4 low and CXCR4 high groups were selected for RNASeq analysis. The progression-free survival (PFS) of CLL patients in the CXCR4 high group was significantly shorter than the CXCR4 low group, with a median follow-up time of 27 months (log-rank P < 0.001). Moreover, CXCR4 overexpression (MFI > 3376) was an independent marker of poor PFS in CLL patients (P < 0.001). Analysis of RNASeq results revealed that CXCR4 plays an important role in the migration of CLL. Collectively, CXCR4 expression levels on leukemia cells can be detected rapidly by FCM. CXCR4 overexpression was significantly associated with poorer prognosis in CLL patients within a shorter follow-up time., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Reports on COVID-19 in peritoneal dialysis (PD) patients are scarce in China. This study aimed to describe the characteristics and outcomes of PD patients with COVID-19 after China abandoned the 'zero-COVID' policy., Methods: This single-centre retrospective study included patients receiving PD who underwent testing for COVID-19 infections between 7 December 2022 and 7 January 2023. Outcomes of interest included factors associated with positive COVID-19 testing result and clinical outcomes including COVID-19-related hospitalisation and severe COVID-19, which were analysed using logistic regression analyses., Results: A total of 349 PD patients (male 53.6%, age 49 ± 13 years old) were included, and 235 patients (67.3%) were infected. There were no significant differences between COVID-19 and non-COVID-19 patients other than higher proportion of vaccinated patients and slow transporters in the patients who tested positive for COVID-19 (44.7% vs. 28.1%, p = 0.003; 8.7% vs. 1.8%, p = 0.03, respectively). Multivariate analysis showed COVID-19 was associated with vaccination (odds ratio (OR): 1.71, 95% confidence interval (CI): 1.02-2.86) and slow transport type (compared with average transport type, OR: 4.52, 95% CI: 1.01-20.21). Among the patients with infection, 38 (16.2%) patients were hospitalised, 18 (7.7%) patients had severe disease and 9 (3.8%) patients died. In multivariate logistic analysis, both age (OR: 1.04, 95% CI: 1.01-1.07; OR: 1.06, 95% CI: 1.02-1.11) and hyponatremia (OR: 5.44, 95% CI: 1.63-18.13; OR: 6.50, 95% CI: 1.77-23.85) were independent risk factors for COVID-19-related hospitalisation and severe disease., Conclusions: Although vaccinated patients were more likely to have tested positive for COVID-19 infection, they appeared to have less severe infection and less need for hospitalisation. Patients who were older with a history of hyponatremia were more likely to experience adverse outcomes from COVID-19., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To identify primary factors contributing to hemodialysis-related headache (HRH) in maintenance hemodialysis (MHD) patients., Methods: Adult outpatients receiving MHD were prospectively enrolled from a hemodialysis (HD) center of a tertiary hospital in China. Twelve dialysis sessions were successively monitored for each patient. HRH is defined as having at least three headache episodes that begin during HD and resolve within 72 h of HD session completion. Blood gas analysis during headache episodes and body composition analysis after dialysis were conducted. Hour-to-hour vital sign variability during dialysis was assessed using the metric of average real variability (ARV). Multivariable logistic regression analysis was conducted to explore the factors triggering HRH., Results: A total of 95 Chinese MHD patients were enrolled, with 92 patients (60.9% were males) included in the final analysis. The mean age of the 92 patients was 59.3 ± 17.5 years, and the median dialysis vintage was 27.1 (12-46.2) months. Among them, 12 patients (13%) complained of 42 headache attacks, and eight (8.7%) were diagnosed with HRH. For eight patients with HRH, headache occurred 100.3 ± 69.5 min after the start of dialysis, with a mean VAS score of 4.3 ± 1 points. The quality of headaches was dull (six patients), pulsating (one patient), or stabbing pain (one patient); all the headaches were bilateral, with one having concomitant vomiting. The intradialysis headache duration and the whole headache duration were 98.8 ± 68.1 and 120 (65-217.5) minutes, respectively. Younger age (OR = 0.844, 95% CI 0.719-0.991, p = 0.039), decreased blood sodium level (OR = 0.309 in the range of 133-142 mmol/L, 95% CI 0.111-0.856, p = 0.024), increased ARV of intradialysis systolic blood pressure (OR = 3.067, 95% CI 1.006-9.348, p = 0.049) and ratio of overhydration to dry weight (OR = 1.990, 95% CI 1.033-3.832, p = 0.040) were found to be independent risk factors for HRH., Conclusions: This study suggested a significant attribution of blood sodium, hydration status and blood pressure variability to HRH., (© 2023. The Author(s).)

(1) Background: Inflammation plays an important role in the onset and progression of acute kidney injury (AKI). Despite this, evidence regarding the prognostic effect of the monocyte-to-lymphocyte ratio (MLR), a novel systemic inflammation marker, among patients with AKI is scarce. This study sets out to investigate the prognostic potential of both baseline and early changes in MLR for short-term mortality among critically ill patients with AKI. (2) Method: Eligible patients with AKI from the Medical Information Mart for Intensive Care IV database were retrospectively analyzed. MLR cutoff values were determined using maximally selected rank statistics and tertiles. The clinical outcomes were 30-day and 90-day mortality in the intensive care unit. A restricted cubic splines model and Cox proportional hazards models were utilized to evaluate the association between the baseline MLR and short-term mortality. Then, the trends in MLR over time were compared between the 30-day survivors and non-survivors using a generalized additive mixed model (GAMM). (3) Result: A total of 15,986 patients were enrolled. Multivariable Cox regression analysis identified baseline MLR ≥ 0.48 as an independent risk factor predicting 30-day mortality (HR 1.33, 95%CI 1.24, 1.45, p < 0.001) and 90-day mortality (HR 1.34, 95%CI 1.23, 1.52, p < 0.001) after adjusting for potential confounders. Similar trends were observed for 30-day and 90-day mortality when tertiles were used to group patients. The restricted cubic splines model revealed a non-linear association between MLR and 30-day and 90-day mortality (both p for non-linear < 0.001, both p for overall < 0.001). The area under the curve of 0.64 for MLR was higher than that of monocytes (0.55) and lymphocytes (0.61). In the subgroup analyses, despite the noted significant interactions, the direction of the observed association between MLR and 30-day mortality was consistent across most prespecified subgroups, except for shock and black ethnicity. The GAMM results highlighted that, as time went on, MLR in the 30-day survival group consistently declined, whereas MLR in the non-survival group rose within 15 days post-ICU admission. The difference between the two groups persisted significantly even after adjusting for confounders ( p = 0.006). (4) Conclusion: A higher baseline MLR was identified as an independent risk factor predicting 30-day and 90-day mortality. The early increase in MLR was associated with high 30-day mortality, suggesting that dynamic monitoring of MLR could potentially better predict survival in critically ill patients with AKI.

Objective: Tunneled-cuffed catheters (TCCs) are frequently used for establishing hemodialysis access for maintenance hemodialysis in older patients with exhausted resources of peripheral vessels. Fibrin sheath formation around the catheter is one of the most common complications of long-term use of indwelling catheter, which may cause the malfunction of the catheter. In this study, we intend to compare the prognosis of two catheter replacement methods, in situ replacement and replacement through a fibrin sheath crevice, with both being assisted by balloon dilation, and to explore the optimal catheter replacement process., Methods: A retrospective study was conducted with 52 patients who underwent a replacement of their TCCs. Among them, 27 cases had their TCC replaced by the modified method of replacement through a fibrin sheath crevice and were referred to as the sheath crevice group, while 25 cases underwent in situ catheter replacement and were referred to as the in situ group. The primary outcome indicators included maximum blood flow in hemodialysis catheter and the urea clearance rate calculated by Kt/V values at the 1, 3, and 6-month follow-ups. The secondary outcomes included dialyzer alarms being set off and catheter-related infections during follow-up., Results: There was no significant difference between the general data of the two groups. There was no massive blood loss during the replacement procedure. Neither were there cardiac tamponade, catheter-associated infections, or other complications. Follow-ups were made 1, 3, and 6 months after the replacement procedure. The sheath crevice group had higher catheter blood flow and Kt/V values at the 6-month follow-up than the in situ group did ([241.85±9.62] mL/min vs. [234.40±11.21] mL/min, P =0.014 and 1.31±0.55 vs. 1.27±0.49, P =0.005, respectively). During the follow-up process, access alarms were reported in 5 patients (three in the in situ group and two in the sheath crevice group) during dialysis. No catheter-associated infection occurred in either group., Conclusion: The catheter replacement method of balloon dilation-assisted catheter insertion through a fibrin sheath crevice is safe and effective, resulting in better long-term catheter blood flow compared with that of in situ catheter replacement., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2023《四川大学学报（医学版）》编辑部 版权所有Copyright ©2023 Editorial Board of Journal of Sichuan University (Medical Sciences).)

Primary hypertrophic osteoarthropathy (PHO) is a hereditary bone disease that is grouped into PHO autosomal recessive 1 (PHOAR1) and PHO autosomal recessive 2 (PHOAR2) due to different causative genes. Data comparing bone microstructure between the two subtypes are scarce. This is the first study to find that PHOAR1 patients had inferior bone microstructure compared with PHOAR2 patients., Purpose: The primary goal of this study was to assess bone microarchitecture and strength in PHOAR1 and PHOAR2 patients and to compare them with age- and sex-matched healthy controls (HCs). The secondary goal was to assess the differences between PHOAR1 and PHOAR2 patients., Methods: Twenty-seven male Chinese PHO patients (PHOAR1 = 7; PHOAR2 = 20) were recruited from Peking Union Medical College Hospital. The areal bone mineral density (aBMD) was assessed by dual-energy X-ray absorptiometry (DXA). Peripheral bone microarchitecture at the distal radius and tibia were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Biochemical markers of PGE2, bone turnover, and Dickkopf-1 (DKK1) were investigated., Results: Compared with HCs, PHOAR1 and PHOAR2 patients had distinctively larger bone geometry, substantially lower vBMD at the radius and tibia, and compromised cortical microstructure at the radius. For trabecular bone, PHOAR1 and PHOAR2 patients showed different changes at the tibia. PHOAR1 patients had significant deficits in the trabecular compartment, resulting in lower estimated bone strength. Conversely, PHOAR2 patients showed a higher trabecular number, narrower trabecular separation, and lower trabecular network inhomogeneity than HCs, translating into preserved or slightly high estimated bone strength., Conclusion: PHOAR1 patients had inferior bone microstructure and strength compared with PHOAR2 patients and HCs. Additionally, this study was the first to find differences in the bone microstructure between PHOAR1 and PHOAR2 patients., (© 2023. The Author(s).)

Background: There is little information on the pharmacokinetics and pharmacodynamics of sacubitril/valsartan (SV) in patients undergoing peritoneal dialysis (PD) complicated with hypertension or heart failure (HF). This study was designed to evaluate the pharmacokinetics and pharmacodynamics of SV in PD patients with complications of hypertension or HF., Methods: This was an open-label and cross-sectional study investigating PD patients diagnosed with hypertension or New York Heart Association Class II-IV HF. The concentrations of valsartan, sacubitril and sacubitrilat (LBQ657) were measured by ultra-performance liquid chromatography tandem mass spectrometry in plasma, urine and peritoneal dialysate samples. Pharmacodynamics were evaluated by comparing changes in mean sitting systolic blood pressure (msSBP), mean sitting diastolic blood pressure (msDBP), mean sitting heart rate, N-terminal-pro B-type natriuretic peptide (NT-proBNP) and left ventricular ejection fraction (LVEF)., Results: Forty patients with PD were enrolled including 27 (67.5%) patients with hypertension, 4 (10%) patients with HF and 9 (22.5%) patients with both hypertension and HF. This study included three treatment cohorts: 50 mg twice daily (BID), 100 mg once daily and 100 mg BID. The plasma maximum drug concentrations in the 100 mg BID group were 1995 ± 1499 ng/mL for valsartan, 171 ± 148 ng/mL for sacubitril and 13 686 ± 7418 ng/mL for LBQ657. The 24-h recovery rate of LBQ657 was 3.77% in urine and 2.23% in peritoneal dialysate. After taking SV, msSBP and msDBP decreased by 19.25 ± 10.32 mmHg and 10.10 ± 8.00 mmHg from baseline, respectively. NT-proBNP decreased by 1436.50 (0.00-18 198.00) from baseline, while LVEF increased by 5.00 (-0.25 to 9.25) from baseline after SV treatment., Conclusions: PD and residual renal function contributed only to a minor degree to the elimination of LBQ657. Additionally, a dose of 100 mg BID SV is safe and effective in patients with PD with complications of hypertension or HF., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: Refractory peritonitis is one of the leading causes of catheter failure in peritoneal dialysis (PD) patients. However, there are no established curative therapies available, and only catheter removal should be performed. Here we present a case series study to illustrate the efficacy of antibiotic lock for PD-associated refractory peritonitis., Materials and Methods: Patients with refractory peritonitis treated with intraperitoneal antibiotics plus antibiotic lock from September 2020 to March 2022 were retrospectively analyzed. Medical cure was identified as a success of treatment., Results: We identified 11 patients, of which 7 (63.64%) had a history of PD-associated peritonitis, with the episode of continuous ambulatory peritoneal dialysis (CAPD) ranging from 1 to 158 months at a median of 36 (9.5, 50.5) months. The dialysis effluent culture showed Gram-positive, Gram-negative bacteria, and was culture-negative in 5, 2, and 4 cases, respectively. The cure rates were 85.71% for culture-positive cases and 25% for culture-negative cases, and the total cure rate was 63.64%. No relevant adverse events occurred, including sepsis., Conclusions: Treatment with the additional antibiotic lock was successful in most cases, especially in those that were culture-positive. Additional antibiotic lock deserves great attention and further investigation in treating PD-associated refractory peritonitis.

Introduction: Vascular calcification (VC) is a common complication of chronic kidney disease (CKD) with poor cardiovascular prognosis. The aim of this study was to explore the impact of VC on blood pressure variability (BPV) in animal models of CKD., Methods: Two optimal modelling methods, adenine high-phosphorus (HP) diet + calcitriol and 5/6 nephrectomy (Nx) + HP diet + calcitriol, for CKD-VC were chosen from the first-step experiment for the next step. A total of 36 male Wistar rats were randomly assigned to the standard-chow, sham-operated, adenine, 5/6Nx, adenine-VC, and 5/6Nx-VC groups. Continuous blood pressure (BP) measurement using the BP-2000 animal noninvasive BP analyser was started at the 9th week for the standard-chow, adenine, and adenine-VC groups and at the 7th week for the sham-operated, 5/6Nx, and 5/6Nx-VC groups. BPV metrics (BPVs), including the difference between maximum and minimum values, standard deviation, coefficient of variation, average real variability, and residuals derived from the generalized linear model of BP, were calculated., Results: The first experiment showed that the use of calcitriol accelerated the progression of VC in CKD rats (the modelling period was shortened from 16 weeks to 4-8 weeks) and confirmed the occurrence of VC at weeks 8 and 6 in the adenine-VC and 5/6Nx-VC groups, respectively. In the second experiment, 13 of 20 hour-to-hour BPVs increased significantly with the development of CKD and VC. BPV differences among the standard-chow, adenine, and adenine-VC groups were mainly due to the differences between the standard-chow and adenine-VC groups (7 of 10 BPVs were significantly different), followed by the differences between the standard-chow and adenine groups (3 of 10). BPV differences among the sham-operated, 5/6Nx, and 5/6Nx-VC groups were caused by the differences between the 5/6Nx-VC and 5/6Nx groups (4 of 10) or the 5/6Nx-VC and sham-operated groups (3 of 10)., Conclusion: An increased BPV is observed in CKD rats, and VC further aggravates the abnormality of BPVs independent of CKD., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Acute kidney injury is a highly common and multifactorial renal disease resulting in significant morbidity and mortality, especially sepsis-induced acute kidney injury. There is no effective therapy available to treat or prevent sepsis-induced acute kidney injury. One of the specialized pro-resolving mediators, Resolvin D1 exhibits special anti-inflammatory effects in several inflammatory disease models, but there is little evidence about the effect and mechanism of Resolvin D1 in sepsis-induced acute kidney injury., Methods: We conducted experiments to explore the effect and mechanism of Resolvin D1 in sepsis-induced acute kidney injury. In vitro, human proximal tubular epithelial cells were used to test the apoptosis ratio, cell viability and reactive oxygen species level. In vivo, C57BL/6 mice were injected with lipopolysaccharide to establish a sepsis-induced acute kidney injury model. Renal function and structure, apoptosis ratio of kidney cells, mitochondrial structure and function and related protein and gene levels were assessed., Results: In vitro, the resolvin D1-treated group showed higher cell viability and lower reactive oxygen species levels and apoptosis ratios than the LPS group. In vivo, Resolvin D1 can not only improve renal function and mitochondrial function but also reduce the apoptosis ratio, while mediating mitochondrial dynamics and inhibiting NF-κB pathway., Conclusions: Resolvin D1 has a good renoprotective effect by maintaining mitochondrial dynamics and inhibiting the NF-κB pathway., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Aims: The aim of this study was to systematically review relevant studies to evaluate the value of urinary interleukin-18 (uIL-18) in predicting acute kidney injury (AKI)., Methods: A comprehensive search of PubMed, Medline, Embase, and Cochrane Library was conducted for literature published up to 1 August 2022. Quality Assessment Tool for Diagnostic Accuracy Studies-2 (QUADAS-2) was applied to assess the literature quality. Then, relevant data were extracted from each eligible study and a random-effects regression model was utilized to pool sensitivity, specificity, and construct summary receiver operating characteristic (SROC) and area under curve (AUC)., Results: Twenty-six studies with 7183 patients were enrolled and relevant information was extracted. The estimated sensitivity and specificity of uIL-18 in the diagnosis of AKI were 0.64 (95% confidence interval (CI): 0.54-0.73) and 0.77 (95%CI: 0.71-0.83), respectively. The pooled diagnostic odds ratio (DOR) was 6.08 (95%CI: 3.63-10.18), and the AUC of uIL-18 in predicting AKI was 0.78 (95%CI: 0.74-0.81). Subgroup analysis showed that uIL-18 in pediatric patients was more effective in predicting AKI than in adults (DOR: 7.33 versus 5.75; AUC: 0.81 versus 0.77)., Conclusions: Urinary IL-18 could be a relatively good biomarker with moderate predictive value for AKI, especially in pediatric patients. However, further research and clinical settings are still needed to validate our findings.

Vascular calcification is commonly observed in chronic kidney disease. The mechanism of how the calcification signal from endothelial cells is transmitted to vascular smooth muscle cells (VSMCs) remains unknown. The aim of the present study was to investigate whether exosomes from HUVECs (HUVEC‑Exos) could regulate VSMC calcification and its potential signaling pathway. HUVEC‑Exos were isolated from HUVECs under no phosphorus (NP) and high phosphorus (HP) conditions. Alizarin Red S staining and calcium (Ca) content analysis were carried out to detect calcification in VSMCs. Proteomics analysis was carried out to detect the differential expression of exosomal proteins. Protein and mRNA levels were measured by western blot analysis and reverse transcription‑quantitative PCR (RT‑qPCR). Exosomes derived from HP‑HUVECs promoted the calcification of VSMCs, as assessed by Alizarin Red S staining, alkaline phosphatase activity assays, Ca content measurements and the increased expression of runt‑related transcription factor 2 and osteopontin. Proteomic analysis detected the upregulation of STAT1 in HP‑exosomes from HUVECs (HUVEC‑Exos) compared with NP‑HUVEC‑Exos, which was also confirmed by western blot analysis and RT‑qPCR. Inhibition of STAT1 expression in VSMCs using fludarabine or knockdown of STAT1 expression using small interfering RNA alleviated the calcification of VSMCs. Furthermore, lithium chloride (Wnt activator) reversed the protective effect of STAT1 inhibition on VSMC calcification, while Dickkopf‑1 (Wnt inhibitor) exerted the opposite effect, suggesting that activation of the Wnt/β‑catenin signaling pathway was involved in STAT1‑mediated VSMC calcification. In conclusion, the present results indicated that exosomal STAT1 derived from HP‑treated HUVECs could promote VSMC calcification, and activation of the Wnt/β‑catenin pathway may be a potential mechanism of the VSMC calcification promoted by exosomes.

The negative effects of obesity on the cardiovascular health have drawn much attention. Weight-adjusted-waist index (WWI) has been proved to reflect weight-independent centripetal obesity. However, the association between WWI and abdominal aortic calcification (AAC) has not been reported before. Using data from National Health and Nutrition Examination Survey 2013-2014, we aimed to determine the relationship of WWI and AAC in adults aged ≥ 40 years. WWI was determined by dividing waist circumference by the square root of weight. AAC was measured by dual-energy X-ray absorptiometry and quantified by Kauppila scores. Severe AAC (SAAC) was defined as an AAC score > 6. We utilized weighed multivariable logistic regression and generalized additive model to explore the independent association between WWI and AAC. Threshold effects were further calculated by two-piecewise linear regression model. 3082 participants were enrolled in our analysis, of which 48.2% were male. WWI was positively associated with AAC scores (β = 0.34, 95% CI 0.05-0.63) and exhibited a nonlinear relationship with SAAC. On the left of the breakpoint (WWI = 11.11), WWI and SAAC were positively associated (OR = 2.86, 95% CI 1.40-5.84), while no such relationship was found on the right (OR = 1.07, 95% CI 0.77-1.48). Our findings indicated that WWI may serve as a simple biomarker of AAC in US adults aged ≥ 40 years., (© 2022. The Author(s).)

Background: Although many studies have proven the beneficial effects of caffeine on human health, the association between caffeine intake and the risk of kidney stones is limited in large epidemiologic studies., Objectives: We aimed to investigate the association between caffeine intake and the risk of kidney stones., Methods: A total of 30,716 participants (with weight numbers of 204, 189, and 886) with a history of kidney stone were included in this analysis. All data were survey-weighted, and corresponding logistic regression models were performed to examine the associations between caffeine intake and the risk of kidney stones., Results: In a fully adjusted model, a per-quartile increase in caffeine intake was associated with a 5.32% decreased risk of kidney stones. In the subgroup analysis, the multivariate-adjusted odds ratios (95% confidence intervals) of the risk of kidney stones for per-quartile increments in caffeine intake were 0.9650 (0.9643, 0.9656) for men, 0.9320 (0.9313, 0.9327) for women, 0.9384 (0.9378, 0.9389) for white race individuals, 1.0281 (1.0270, 1.0292) for nonwhite race individuals, 0.9460 (0.9455, 0.9465) for overweight/obese individuals, and 0.9314 (0.9303, 0.9324) for non-overweight individuals, 0.9100 (0.9094, 0.9105) for caffeine from coffee, and 1.0021 (1.0013, 1.0029) for caffeine from non-coffee sources., Conclusion: Caffeine intake was negatively associated with the risk of kidney stones. In subgroup analyses, the negative association of caffeine with kidney stone risk was only found in white individuals. In addition, the decreased risk was found higher in women and non-overweight individuals. Especially for women, white individuals and non-overweight individuals. The protective effect of caffeine intake from coffee on stone formation was more significant than that of caffeine from non-coffee sources., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Geng, Qiu, Kang, Li, Li, Liao, Qin, Yang and Su.)

Background: The negative effects of visceral adiposity accumulation on cardiovascular health have drawn much attention. However, the association between the Visceral Adiposity Index (VAI) and Abdominal Aortic Calcification (AAC) has never been reported before. The authors aimed to investigate the association between the VAI and AAC in US adults., Methods: Cross-sectional data were derived from the 2013 to 2014 National Health and Nutrition Examination Survey (NHANES) of participants with complete data of VAI and AAC scores. Weighted multivariable regression and logistic regression analysis were conducted to explore the independent relationship between VAI and AAC. Subgroup analysis and interaction tests were also performed., Results: A total of 2958 participants were enrolled and participants in the higher VAI tertile tended to have a higher mean AAC score and prevalence of severe AAC. In the fully adjusted model, a positive association between VAI and AAC score and severe AAC was observed (β = 0.04, 95% CI 0.01‒0.08; OR = 1.04, 95% CI 1.01‒1.07). Participants in the highest VAI tertile had a 0.41-unit higher AAC score (β = 0.41, 95% CI 0.08‒0.73) and a significantly 68% higher risk of severe AAC than those in the lowest VAI tertile (OR = 1.68, 95% CI 1.04‒2.71). Subgroup analysis and interaction tests indicated that there was no dependence for the association of VAI and AAC., Conclusion: Visceral adiposity accumulation evaluated by the VAI was associated with a higher AAC score and an increased likelihood of severe AAC., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: Iron deficiency is common in patients with end-stage renal disease (ESRD). Platelet count changes may reflect iron status, but the relationship between platelet count and iron indices is unclear in patients with ESRD., Methods: We conducted a retrospective study in 1,167 patients with ESRD from 2012 to 2017 in West China Hospital. Baseline data were used to analyze the relationship between the platelet count and iron indices. Patients were followed up for 3 years., Results: Patients with iron deficiency (both absolute and functional) had a higher platelet count than those without iron deficiency (174 ± 61 × 10 9 /L vs. 153 ± 58 × 10 9 /L, P < .001). Receiver operating characteristic analysis showed a weak predictive power of platelet count on absolute iron deficiency (area under curve 0.620; cutoff value > 137 × 10 9 /L, sensitivity 76%, specificity 43%) and functional iron deficiency (area under curve 0.540; cutoff value > 124 × 10 9 /L, sensitivity 77%, specificity 32%). Platelet count was negatively correlated with ferritin (Spearman's rho [ρ] -0.1547, P < .001), transferrin saturation (ρ = -0.1895, P < .001), and serum iron (ρ = -0.1466, P < .001). The abovementioned correlations remained significant in multivariate regression (β -0.7285, 95% confidence interval [CI] -1.0757 to -0.3814; β -.00347, 95% CI -0.0520 to -0.0174; β -0.0097, 95% CI -0.0159 to -0.0035, respectively). In unadjusted and adjusted Cox regression models, neither baseline platelet count nor relative thrombocytosis was associated with 3-year mortality., Conclusion: There was a weak but significant platelet count elevation in patients with ESRD and with iron deficiency., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Coronary chronic total occlusion (CTO) contributes to the progression of heart failure in patients with ischemic cardiomyopathy. Randomized controlled trials demonstrated that percutaneous coronary intervention (PCI) for CTO significantly improves angina symptoms and quality of life but fails to reduce clinical events compared with optimal medical therapy. Even so, intervening physicians strongly support CTO-PCI. Cardiac regeneration therapy after CTO-PCI should be a promising approach to improving the prognosis of ischemic cardiomyopathy. However, the relationship between CTO revascularization and cardiac regeneration has rarely been studied, and experimental studies on cardiac regeneration usually employ rodent models with permanent ligation of the coronary artery rather than reopening of the occlusive artery. Limited early-stage clinical trials demonstrated that cell therapy for cardiac regeneration in ischemic cardiomyopathy reduces scar size, reverses cardiac remodeling, and promotes angiogenesis. This review focuses on the status quo of CTO-PCI in ischemic cardiomyopathy and the clinical prospect of cardiac regeneration in this setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liao, Li, Wang, Lin and Sun.)

Aims: The negative effect of obesity on kidney health has been reported. The association between weight-adjusted-waist index (WWI, a newly developed adiposity index) and albuminuria has not been reported earlier., Methods: This cross-sectional study was conducted among adults with complete data about WWI and urinary albumin-to-creatinine ratio (ACR) in 2005-2018 National Health and Nutrition Examination Survey (NHANES). WWI was calculated as waist circumference (WC) divided by the square root of weight. Weighted multivariable logistic regression and generalized additive model were employed to explore the independent relationship between WWI with albuminuria and its non-linearity. A two-piecewise linear regression model was used to calculate the threshold effect. Subgroup analysis and interaction tests were also performed., Results: A total of 36,921 participants were enrolled with a prevalence of albuminuria of 9.32%. The prevalence of albuminuria increased with the higher WWI tertiles (Tertile 1: 5.31%, Tertile 2: 8.23%, Tertile 3: 15.65%). WWI was positively associated with a higher likelihood of albuminuria (OR = 1.28, 95% CI: 1.15-1.43), and this relationship remains stable in subgroups (all P for trend > 0.05). Non-linear positive relationships were detected in females with a breakpoint of 10.93. A positive association between WWI and albuminuria (OR = 1.39, 95% CI: 1.20-1.61) was observed on the right of the breakpoint, while the association on the left was of no statistical significance. WWI showed a stronger correlation with albuminuria (OR = 1.28) than other markers of obesity including body mass index (BMI, OR = 1.02) and WC (OR = 1.01)., Conclusion: Weight-adjusted-waist index levels were positively related to an increased likelihood of albuminuria in United States adults and showed a stronger relationship than BMI and WC. Our findings indicated that WWI may serve as a simple anthropometric index to predict albuminuria., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qin, Chang, Yang, Yu, Liao and Su.)

Aims: This study aimed to evaluate the association between blood cadmium concentration (BCC) and abdominal aortic calcification (AAC) in adults aged ≥40 years in the United States., Methods: Data were obtained from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). Participants without data about BCC and AAC scores were excluded. BCC was directly measured using inductively coupled plasma mass spectrometry (ICP-MS). AAC scores were quantified by the Kauppila scoring system, and severe AAC was defined as an AAC score >6. Weighted multivariable regression analysis and subgroup analysis were conducted to explore the independent relationship between cadmium exposure with AAC scores and severe AAC., Results: A total of 1,530 participants were included with an average BCC of 0.47 ± 0.02 μg/L and AAC score of 1.40 ± 0.10 [mean ± standard error (SE)]. The prevalence of severe AAC was 7.96% in the whole subjects and increased with the higher BCC tertiles (Tertile 1: 4.74%, Tertile 2: 9.83%, and Tertile 3: 10.17%; p = 0.0395). We observed a significant positive association between BCC and the AAC score (β = 0.16, 95% CI : 0.01~0.30) and an increased risk of severe AAC [odds ratio (OR) = 1.45; 95% CI : 1.03~2.04]. Subgroup analysis and interaction tests revealed that there was no dependence for the association between BCC and AAC., Conclusion: Blood cadmium concentration was associated with a higher AAC score and an increased likelihood of severe AAC in adults in the United States. Cadmium exposure is a risk factor for AAC, and attention should be given to the management of blood cadmium., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qin, Liu, Jiao, Geng, Liao and Su.)

Background: Systemic immune-inflammation index (SII) is a novel inflammatory marker, and inflammation has been reported to be related with renal damage. We aimed to investigate the possible relationship between SII and albuminuria., Methods: The present cross-sectional study was conducted among adults with complete data about SII and urinary albumin-to-creatinine ratio (ACR) in 2005-2018 National Health and Nutrition Examination Survey (NHANES). SII was calculated as the platelet count × neutrophil count/lymphocyte count. Albuminuria was defined as ACR >30mg/g. Weighted multivariable regression analysis and subgroup analysis were conducted to explore the independent relationship between SII and albuminuria., Results: A total of 36,463 individuals were included in our analysis; 9.56% participants were categorized as having albuminuria overall and increased with the higher SII tertiles (tertile 1, 7.83%; tertile 2, 8.49%; tertile 3, 12.13%; p for trend <0.0001). Multivariable logistic regression showed that a higher SII level was associated with increased likelihood of albuminuria independently (OR = 1.31; 95% CI, 1.17-1.48, p<0.0001) after full adjustment. Subgroup analysis and interaction test showed that there was no significant dependence of gender, age, body mass index, hypertension, diabetes, non-alcoholic fatty liver disease, and estimated glomerular filtration rate (eGFR) on this positive association (all p for interaction >0.05)., Conclusions: SII was positively associated with increased urinary albumin excretion in US adults. Further large-scale prospective studies are still needed to analyze the role of SII in albuminuria., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qin, Li, Wang, Geng, Yang, Su and Liao.)

Background: Although many molecular studies have tried to explore the relationship between vitamin D metabolism and kidney function, the association between 25-hydroxyvitamin D [25(OH)D] and kidney function is still controversial. Previous studies reported that low vitamin D status and decreased kidney function were associated with insulin resistance (IR). However, neither of them was confirmed by large population-based studies. This study evaluated the associations between 25(OH)D and kidney function and the associations between both of them and IR among adults in the United States of America (USA)., Methods: We analyzed 36,523 adults from the National Health and Nutrition Examination Survey (NHANES) (2001-2014). Kidney function was assessed by the estimated glomerular filtration rate (eGFR), and IR was assessed by homeostasis model assessment (HOMA-IR). All data were survey-weighted, and corresponding linear regression models were performed to examine the associations., Results: The mean serum 25(OH)D levels were found to be increased in participants with decreased kidney function (eGFR <90 ml/min/1.73 m 2 ), and each unit of decreased serum 25(OH)D concentrations predicted 0.453 ml/min/1.73 m 2 (95% CI: 0.426 to 0.480, p < 0.0001) higher eGFR. In addition, each unit of decreased eGFR was associated with 0.007 higher HOMA-IR, while each unit of decreased 25(OH)D concentrations led to 0.025 higher HOMA-IR., Conclusions: Serum 25-hydroxyvitamin D concentrations were negatively associated with kidney function. IR appears in the early stage of kidney dysfunction, and both serum 25(OH)D concentrations and kidney function are negatively associated with IR. Clinicians should maintain appropriate serum 25(OH)D concentrations and doses of vitamin D supplements for different populations. The underlying mechanism of these associations still needs more research, especially the negative association between serum 25(OH)D concentrations and kidney function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Geng, Qiu, Li, Li, Liao, Du, Jiang, Wang, Qin, Yang, Yu, Zhang and Su.)

Right ventricular infarction (RVI) is a common presentation in clinical practice. Severe RVI can lead to fatal hemodynamic dysfunction and arrhythmia. In contrast to the extensively used mouse myocardial infarction (MI) model generated by left coronary artery ligation, the RVI mouse model is rarely employed due to the difficulty associated with model generation. Research on the mechanisms and treatment of RVI-induced RV remodeling and dysfunction requires animal models to mimic the pathophysiology of RVI in patients. This study introduces a feasible procedure for RVI model generation in C57BL/6J mice. Further, this model was characterized based on the following: infarct size evaluation at 24 h after MI, assessment of cardiac remodeling and function with echocardiography, RV hemodynamics assessment, and histology of the infarct zone at 4 weeks after RVI. In addition, a coronary vasculature cast was performed to observe the coronary arterial arrangement in RV. This mouse model of RVI would facilitate the research on mechanisms of right heart failure and seek new therapeutic targets of RV remodeling.

Aims: We aimed to assess the association between triglyceride-glucose (TyG) index and kidney stones in US adults., Methods: Data were obtained from the 2007-2014 National Health and Nutrition Examination Survey (NHANES). Participants aged ≥18 years who were not pregnant and provided complete data about TyG index and kidney stones were included in the analysis. Weighted multivariable regression analysis and subgroup analysis were preformed to estimate the independent relationship between TyG index and nephrolithiasis and recurrence., Results: A total of 20,972 participants were included with the mean TyG index of 8.71 ± 0.72. The prevalence rates of nephrolithiasis and recurrence were 9.30% and 3.17% overall and increased with the higher TyG index tertiles (Nephrolithiasis: Tertile 1, 6.98%; Tertile 2, 9.15%; Tertile 3, 11.98%, p < 0.01; Recurrence: Tertile 1, 1.84%; Tertile 2, 3.27%; Tertile 3, 4.50%, p < 0.01). Each unit increase in TyG index was associated with 12% and 26% higher odds of nephrolithiasis [odds ratio (OR) = 1.12; 95% CI: 1.02-1.22; p = 0.02] and recurrence (OR = 1.26; 95% CI: 1.08-1.46; p < 0.01). Interaction tests indicated no significant effect of gender, age, body mass index, hypertension, and diabetes on this association between TyG index and kidney stones., Conclusions: Higher TyG index was associated with an increased likelihood of nephrolithiasis and recurrence. Considering TyG index is a reliable indicator of insulin resistance (IR). Treatment and management of IR at a younger age may improve or alleviate the occurrence and recurrence of kidney stones., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qin, Zhao, Geng, Chang, Liao and Su.)

Aims: This study aimed to evaluate the association between blood lead level (BLL) and abdominal aortic calcification (AAC) in US adults aged ≥40 years. Methods: We obtained data from 2013 to 2014 National Health and Nutrition Examination Survey (NHANES). Participants missing the data of BLL and AAC scores were excluded. BLL was measured using inductively coupled plasma mass spectrometry directly. AAC scores were quantified by Kauppila score system, and severe AAC was defined as AAC score >6. Weighted multivariable regression analysis and subgroup analysis were conducted to explore the independent relationship between BLL with AAC score and severe AAC. Results: A total of 1,530 participants were included with the mean BLL of 1.45 ± 1.31 ng/dl and mean AAC score of 1.40 ± 3.13. The prevalence of severe AAC was 7.98% overall, and participants in higher BLL quartile showed higher prevalence of severe AAC (Quartile 1: 3.55%, Quartile 2: 7.28%, Quartile 3: 9.88%, Quartile 4: 12.58%, P < 0.0001). BLL was positively associated with higher AAC score (β = 0.15, 95% CI: 0.02, 0.27, P = 0.021) and increased risk of severe AAC (OR = 1.11; 95% CI: 1.00-1.22; P = 0.047). Subgroup analysis and interaction test indicated that the association between BLL and AAC was similar in different population settings. Conclusions: Higher BLL was associated with higher AAC score and increased risk of severe AAC. Lead burden should be considered for people with AAC in clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qin, Li, Xu, Li, Su and Liao.)

We investigated the relationship between low lean mass (LLM) and lower urinary tract symptoms (LUTS) using the 2005-2006 National Health and Nutrition Examination Survey (NHANES) dataset. We enrolled 959 men with an average age of 52.08 ± 7.91 years and performed weighted multiple regression analysis to determine the independent relationship between exposure variables (LLM, alternate LLM) and outcomes variables (urinary hesitancy, incomplete emptying, urinary frequency, nocturia, daytime LUTS, clinical LUTS) after adjusting for confounding factors. The prevalence of urinary hesitancy (OR = 7.76, P < 0.0001), incomplete emptying (OR = 2.49, P = 0.0070), urinary frequency (OR = 3.28, P < 0.0001), daytime LUTS (OR = 3.88, P < 0.0001) and clinical LUTS (OR = 8.11, P < 0.0001) was significantly higher among men with LLM compared to men without LLM. Moreover, alternate LLM (ALLM) was positively associated with urinary hesitancy (OR = 17.97, P < 0.0001), incomplete emptying (OR = 4.68, P = 0.0003), daytime LUTS (OR = 2.47, P = 0.0136) and clinical LUTS (OR = 12.18, P < 0.0001). These findings demonstrate that both LLM and ALLM were associated with a higher risk of LUTS in men aged ≥ 40 years, which suggested that early management and treatment of lean mass loss may improve or alleviate LUTS.

Background: We explored the associations between serum leptin concentration and cardiovascular prognosis in maintenance hemodialysis patients., Methods: In our prospective study with no intervention, demographics data at baseline were collected from electronic medical records. Serum leptin concentration was determined by ELISA. Patients underwent body composition assessment and echocardiographic measurements after hemodialysis. The primary endpoints were defined as cardiovascular events (CVEs), cardiovascular death (CVD) and all-cause death., Results: A total of 165 eligible patients aged 51(43-65) y were enrolled and the mean serum leptin concentration was 35.49 (29.98) ng/ml. During a median follow-up of 18 (12-22) months, CVEs occurred in 37 (22.42%) patients and the cardiovascular and all-cause mortality was 10.91% and 21.82%. Serum leptin concentration was associated with CVEs (HR = 0.982, p = 0.003), CVD (HR = 0.934, p = 0.002) and all-cause death (HR = 0.943, p < 0.001). Decreased serum leptin concentration was an independent risk factor for the development of left ventricular hypertrophy (LVH, OR = 0.98, p = 0.007) and peripheral vascular disease (PVD, OR = 0.974, p = 0.007)., Conclusion: Serum leptin concentration can independently predict cardiovascular outcomes and all-cause death in MHD patients. The effects that serum leptin concentration on development of LVH and PVD maybe the potential mechanism., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: We aimed to assess the association between dietary inflammation index (DII) and abdominal aortic calcification (AAC) in US adults aged ≥40 years. Methods: Data were obtained from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). Participants who were <40 years old and missing the data of DII and AAC were excluded. DII was calculated based on a 24-h dietary recall interview for each participant. AAC score was quantified by assessing lateral spine images and severe AAC was defined as AAC score >6. Weighted multivariable regression analysis and subgroup analysis were preformed to estimate the independent relationship between DII with AAC score and severe AAC. Results: A total of 2,897 participants were included with the mean DII of -0.17 ± 2.80 and the mean AAC score of 1.462 ± 3.290. The prevalence of severe AAC was 7.68% overall, and participants in higher DII quartile tended to have higher rates of severe AAC (Quartile 1: 5.03%, Quartile 2: 7.44%, Quartile 3: 8.38%, Quartile 4: 10.46%, p = 0.0016). A positive association between DII and AAC score was observed (β = 0.055, 95% CI: 0.010, 0.101, p = 0.01649), and higher DII was associated with an increased risk of severe AAC (OR = 1.067, 95% CI: 1.004, 1.134, p = 0.03746). Subgroup analysis indicated that this positive association between DII and AAC was similar in population with differences in gender, age, BMI, hypertension status, and diabetes status and could be appropriate for different population settings. Conclusion: Higher pro-inflammatory diet was associated with higher AAC score and increased risk of severe AAC. Anti-inflammatory dietary management maybe beneficial to reduce the risk of AAC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qin, Chang, Liao, Jiang, Yang and Su.)

Aims: This study aimed to assess the relationship between dietary inflammatory index (DII) and sex hormones in male children and adolescents aged 6-19 years., Methods: We obtained data from the 2013-2016 National Health and Nutrition Examination Survey (NHANES). Male participants aged 6-19 years old with the complete data of DII and sex hormones were included. Weighted multiple regression analysis and subgroup analysis were preformed to estimate the independent relationship between DII and sex hormones., Results: A total of 1717 male participants with the average age of 13.02 ± 3.82 years were enrolled, of whom 41.3% (n=713) were children and 58.47% (n=1004) were adolescents. In children, mean DII was 0.18 ± 1.67, with scores ranging from -4.53 to 4.08. As for adolescents, the mean DII was 0.36 ± 1.98, mean total testosterone (TT) was 376.94 ± 206.69 ng/dl overall. A negative association between DII with TT and estradiol (E2) was observed (TT: β=-11.97, P=0.0006; E2: β=-0.45, P=0.0108) in male adolescent. Subgroup analysis and interaction test results indicated that this association was similar in male adolescents with different body mass index. No statistically significant association was observed in children., Conclusions: Pro-inflammatory diet was associated with lower TT and E2 level in male adolescent, while no association with statistical significance between them was observed in male children. However, more studies are still needed to validate the causal relationship between DII and sex hormones., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qin, Liu, Liao, Jiang and Su.)

Aims: We aimed to assess the association between dietary inflammation index (DII) with parathyroid hormone (PTH) and hyperparathyroidism (HP) in adults with/without chronic kidney disease (CKD). Methods: Data were obtained from the 2003-2006 National Health and Nutrition Examination Survey (NHANES). The participants who were <18 years old, pregnant, or missing the data of DII, PTH, and CKD were excluded. DII was calculated based on a 24-h dietary recall interview for each participant. Weighted multivariable regression analysis and subgroup analysis were conducted to estimate the independent relationship between DII with PTH and the HP in the population with CKD/non-CKD. Results: A total of 7,679 participants were included with the median DII of -0.24 (-2.20 to 1.80) and a mean PTH level of 43.42 ± 23.21 pg/ml. The average PTH was 45.53 ± 26.63 pg/ml for the participants in the highest tertile group compared with 41.42 ± 19.74 pg/ml in the lowest tertile group ( P < 0.0001). The rate of HP was 11.15% overall, while the rate in the highest DII tertile was 13.28 and 8.60% in the lowest DII tertile ( P < 0.0001). The participants with CKD tended to have higher PTH levels compared with their counterparts (61.23 ± 45.62 vs. 41.80 ± 19.16 pg/ml, P < 0.0001). A positive association between DII scores and PTH was observed (β = 0.46, 95% CI: 0.25, 0.66, P ≤ 0.0001), and higher DII was associated with an increased risk of HP (OR = 1.05, 95% CI: 1.02, 1.08, P = 0.0023). The results from subgroup analysis indicated that this association was similar in the participants with different renal function, gender, age, BMI, hypertension, and diabetes statuses and could also be appropriate for the population with CKD. Conclusions: Higher consumption of a pro-inflammatory diet appeared to cause a higher PTH level and an increased risk of HP. Anti-inflammatory dietary management may be beneficial to reduce the risk of HP both in the population with and without CKD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qin, Yang, Liao and Su.)

Objectives: The aim of this study is to compare the prognostic effects of visceral fat area (VFA) with coronary artery calcification score (CACs) in patients on maintenance hemodialysis., Design and Methods: In the prospective study with no intervention, clinical characteristics and serum biochemical indexes at baseline for each patient were collected through the electronic medical records. Body composition assessment using bioelectrical impedance analysis, computed tomography examination with the Agatston scoring method, and echocardiographic measurements were performed at enrollment. Primary endpoints included cardiovascular events (CVEs), cardiovascular death (CVD), and all-cause death., Results: A total of 97 Chinese patients aged 48 (35-62) years were enrolled from our Hemodialysis Center, of which 61.9% were male and 20.6% had diabetes. The median of VFA and CACs at baseline was 64.5 (43.5-88.7) cm 2 and 0.9 (0-467.6), respectively. CVEs occurred in 20 (20.6%) patients during a median follow-up of 26.4 (13-27.7) months. The cardiovascular and all-cause mortality was 8.2% (8 patients) and 11.3% (11 patients), respectively. VFA was associated with CVEs (hazard ratio [HR] = 9.21 for VFA ≥71.3 cm 2 vs. VFA <71.3 cm 2 , P = .017), CVD (HR = 1.11 for 1 cm 2 increase, P = .035), and all-cause mortality (HR = 1.08 for 1 cm 2 increase, P = .011). Also, VFA was significantly correlated with cardiac structure parameters and the development of left ventricular hypertrophy (odds ratio = 1.02 for 1 cm 2 increase, P = .03). Yet, CACs were not correlated with CVEs, CVD, or all-cause mortality., Conclusions: Increased VFA can be used as an independent predictor for CVEs, CVD, and all-cause mortality. The effect VFA exerts on cardiac reconstruction might be the underlying mechanism. Further studies are warranted for the management of VFA in the hemodialysis population., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Vascular calcification (VC) is the abnormal deposition of calcium, phosphorus, and other minerals in the vessel wall and can be commonly observed in diabetes, chronic kidney disease, and chronic inflammatory disease. It is closely associated with mortality from cardiovascular events. Traditionally, calcification is considered as a degenerative disease associated with the aging process, while increasing evidence has shown that the occurrence and development of calcification is an active biological process, which is highly regulated by multiple factors. The molecular mechanisms of VC have not yet been fully elucidated. Exosomes, as important transporters of substance transport and intercellular communication, have been shown to participate in VC. The regulation of VC by exosomes involves a number of complex biological processes, which occur through a variety of interaction mechanisms. However, the specific role and mechanism of exosomes in the process of VC are still not fully understood and require further study. This review will briefly describe the roles of exosomes in the process of VC including in the promotion of extracellular mineral deposits, induction of phenotypic conversion of vascular smooth muscle cells (VSMCs), transport of microRNA between cells, and regulation on autophagy and oxidative stress, with the aim of providing novel ideas for the clinical diagnosis and treatment of VC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-7355). BS serves as an unpaid editorial board member of Annals of Translational Medicine from Sep 2020 to Aug 2021. The authors have no other conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection and is associated with high morbidity and mortality. Circulating histones (CHs), a group of damage-associated molecular pattern molecules mainly derived from neutrophil extracellular traps, play a crucial role in sepsis by mediating inflammation response, organ injury and death through Toll-like receptors or inflammasome pathways. Herein, we first elucidate the molecular mechanisms of histone-induced inflammation amplification, endothelium injury and cascade coagulation activation, and discuss the close correlation between elevated level of CHs and disease severity as well as mortality in patients with sepsis. Furthermore, current state-of-the-art on anti-histone therapy with antibodies, histone-binding proteins (namely recombinant thrombomodulin and activated protein C), and heparin is summarized to propose promising approaches for sepsis treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Wan, Luo, Song, Wang, Yu, Jiang, Liao, Zhao and Su.)

Aim: Vascular calcification (VC) is a common complication in chronic kidney disease (CKD) and has been shown to be associated with increased cardiovascular events and mortality. This study was to explore the role of Wnt-signaling pathway in CKD VC, and the association between VC and blood pressure variability (BPV) which is a risk factor of cardiovascular events., Methods: Adult male Sprague-Dawley rats were divided into adenine-induced CKD group (n = 5), 5/6 nephrectomy CKD group (n = 5), sham group (n = 5) and control group (n = 5). Low-calcium-high-phosphate diets were introduced to induce vascular calcification. Both daytime (hour-to-hour during the day) and mid-term (day-to-day for 9 days) blood pressure (BP) were collected and analyzed for BPV metrics. At sacrifice, kidney, heart and aorta samples were taken for histological analyses. Calcium deposition in aorta was identified with Alizarin Red stain and graded. Immunohistochemistry stain and western blot were performed for Wnt3a, Wnt5a, β-catenin, sclerostin, osteopontin, and α-SMA., Results: Compared with control rats, CKD rats suffered from markedly severer VC (Grade 2.6 ± 0.2 and 1.8 ± 0.8 vs 0.0 ± 0.0 and 0.2 ± 0.4, P = .0010). VC was positively correlated with vascular Wnt3a and β-catenin expression (P = .0032 and .0000), but not significantly associated with Wnta5a or sclerostin. Besides, CKD rats showed increased BPV (P < .001), which was also positively correlated with VC., Conclusion: We confirmed that CKD rats had enhanced Wnt-signaling in vascular tissue and severer aorta calcification together with increased BPV. Wnt pathway may be a potential target in future VC and BPV management in CKD., (© 2019 Asian Pacific Society of Nephrology.)

Coronary artery calcifications (CACs) are common among maintenance hemodialysis (MHD) patients and associated with increased morbidity and mortality due to cardiovascular events. The insight into chronic kidney disease-mineral and bone disorder (CKD-MBD) established a correlation between dysregulated mineral metabolism and CACs. This study aimed to identify the association of mineral content outside of bone (MCOB) with CACs and cardiovascular events in MHD patients. In the pilot prospective study with no intervention, patients underwent body composition assessment by body composition monitor after hemodialysis and computed tomography examination using the Agatston scoring method simultaneously within a week. The primary end point included cardiovascular events and cardiovascular death. Correlations and receiver operating characteristic analysis elucidated the associations of MCOB with CACs; multivariate analysis assessed the cardiovascular risk for groups with different MCOB. One hundred three eligible patients with an average age of 48 (35-63) years old were enrolled and followed up to 12 (11-12.5) months, among which 52.4% had detectable CACs at baseline. MCOB showed an inverse correlation with Agatston score and significantly discriminated the patients with Agatston score > 0 (AUC = 0.737; P < 0.001) and 400 (AUC = 0.733; P < 0.001). MCOB ≤ 9.2657 mg/kg was an independent risk factor for CACs (OR = 4.853; P = 0.044) and strong predictor for cardiovascular morbidity and mortality (HR = 10.108; P = 0.042), as well as rehospitalization (HR = 2.689; P = 0.004). MCOB inversely correlated with the presence and extent of CACs, and could discriminate Agatston score > 0 and 400, which also presented as an independent indicator for CKD-MBD and 1-year cardiovascular prognosis in adult MHD patients. Additional studies are required for identifying this issue., (© 2019 The Authors. Artificial Organs published by Wiley Periodicals, Inc. on behalf of International Center for Artificial Organ and Transplantation (ICAOT).)

Arteriovenous fistula (AVF) strategy has been recommended in clinical guidelines for a long time due to the survival benefits associated with it. However, the underlying mechanism still needs to be explored. This retrospective cohort study included 611 patients who received hemodialysis in West China Hospital Medical Center between January 1, 2014 and December 31, 2014. Patient characteristics, dialysis parameters, and 1-year blood pressure records were collected at baseline. Echocardiographic changes and clinical outcomes were assessed during the 59-month follow-up. Our study showed that fistulas were associated with lower long-term systolic blood pressure (SBP) standard deviation (SD) (P < 0.0001), lower long-term SBP residual metric (P < 0.0001), and lower intradialytic SBP residual (P = 0.001). Fistulas were also associated with a higher but non-significant proportion of the newly developed left ventricular (LV) hypertrophy (8.29% vs. 6.78%, P = 0.116) and increased LV volume (8.29% vs. 4.52%, P = 0.139), as well as a lower proportion of the newly developed left ventricular ejection fraction (LVEF) dysfunction (1.62% vs. 2.82%, P = 0.586). After a median of 59-month follow-up, catheter group showed a higher risk of cardiovascular events (hazard ratio [HR] 1.21; 95% confidence interval [95%CI] 1.01-1.52), all-cause infection (HR 1.25; 95%CI 1.07-1.47), and access-related infection (HR 2.88; 95%CI 1.76-4.68). However, the advantage of fistulas only retained in low-albumin subgroup (serum albumin < 40 g/l) except for access-related infections. Our results suggested the possible attribution of BPV and other patient factors to fistula-associated survival benefits.

Background: This study aimed to investigate whether hemodialysis (HD) affects tissue factor (TF), tissue factor pathway inhibitor (TFPI), and polymorphonuclear elastase (PMNE) in endstage renal disease (ESRD) patients when eliminating the effects of heparin. Also, to explore the interaction of TF, TFPI, and PMNE throughout a single HD session., Methods: We enrolled 57 ESRD patients who had undergone hemodialysis for >3 months as an experimental group. Plasma levels of TF, TFPI and PMNE were measured by ELISA in 24 ERSD patients on intermittent HD using low-molecular-weight heparin (LMWH) as anticoagulation (LMWH group) and 33 ESRD patients using citrate as anticoagulation (citrate group) at the start and at 1, 2 and 5 h of the HD session. Meanwhile,28 ESRD patients not on dialysis were enrolled as a control group and fasting venous blood samples were taken in the morning., Results: Compared with the control group, the plasma TFPI levels of the LMWH group and the citrate group were significantly higher (P=0.000, P=0.002, respectively) under baseline conditions as well as the plasma PMNE levels (P=0.001, P=0.02, respectively), whereas TF showed no difference (P=0.186). During HD with citrate, plasma TFPI decreased slightly (P=0.012) and PMNE increased significantly (P=0.008) at 1 h. The plasma TFPI levels of the citrate group correlate with PMNE at 2 and 5 h (P=0.001, P=0.008, respectively)., Conclusions: ESRD patients on HD have significantly higher TFPI and PMNE levels compared to patients not on HD under baseline conditions, while TF levels were similar between the three groups. TFPI and PMNE are differently regulated, but the plasma levels correlated during HD in the citrate group. It might be possible that PMNE plays a role in anticoagulative activity through TFPI., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a common complication in patients experiencing end-stage renal disease (ESRD). It includes abnormalities in bone and mineral metabolism and vascular calcification. Hyperphosphatemia is a major risk factor leading to morbidity and mortality in patients with chronic kidney disease. Increased mortality has been observed in patients with ESRD, with serum phosphorus levels of >5.5 mg/dL. Therefore, control of hyperphosphatemia is a major therapeutic goal in the prevention and treatment of CKD-MBD. The treatment of hyperphosphatemia includes decreasing intestinal phosphorus load and increasing renal phosphorus removal. Decreasing the intestinal load of phosphorus plays a major role in the prevention and treatment of CKD-MBD. Among the dietary sources of phosphorus, some of the commonly prescribed medications have also been reported to contain phosphorus. However, drugs are often ignored even though they act as a potential source of phosphorus. Similarly, although proteins are the major source of dietary phosphorus, reducing protein intake can increase mortality in patients with CKD. Recently, the importance of phosphorus/protein ratio in food have been reported to be a sensitive marker for controlling dietary intake of phosphorus. This review summarizes the progress in the research on phosphate content in drugs as an excipient and the various aspects of dietary management of hyperphosphatemia in patients with CKD, with special emphasis on dietary restriction of phosphorus with low dietary phosphate/protein ratio.

Background: Blood pressure variability (BPV) is a potential prognostic predictor for all-cause mortality., Objectives: We conducted a retrospective cohort study to compare the prognostic value of long-term BPV with intra-dialytic BPV in hemodialysis (HD) patients., Materials and Methods: We included 611 HD patients and collected their baseline blood pressure (BP) measurements for 1 year and monitored them for 40 months. Long-term BPV was assessed by pre-dialysis BP SD and pre-dialysis absolute BP residual metric. Intra-dialytic BPV was assessed by intra-dialytic BP average real variability and intra-dialytic absolute BP residual., Results: Long-term systolic BPV showed a weak correlation with mean BP, but a stronger correlation with intra-dialytic BPV. High long-term systolic blood pressure (SBP) SD and long-term SBP residual metrics were associated with high all-cause mortality (p = 0.0084 and 0.0056, respectively), while no such association was found for intra-dialytic BPV or diastolic BPV. According to receiver operating characteristic curve with mortality as dependent variable, long-term SBP residual metric showed the strongest prognostic ability (area under curve [AUC] 0.679, p = 0.0006), which was even stronger in patients with BP ≥140/90 mm Hg (AUC 0.713, p = 0.0004). After completely adjusting for confounders, long-term SBP residual metric remained significantly associated with all-cause mortality (hazard ratio 1.628 per quartile; 95% CI 1.086-2.441)., Conclusions: Our results suggest long-term SBP residual metric to be a better predictor of all-cause mortality in HD patients, which could be used as an additional target for BP management., (© 2019 S. Karger AG, Basel.)

Primary hypertrophic osteoarthropathy (PHO) is an inherited disease characterized by digital clubbing, periostosis, and pachydermia. Based on two causative genes, hydroxyprostaglandin dehydrogenase (HPGD) and solute carrier organic anion transporter family member 2A1 (SLCO2A1), PHO is categorized into two subtypes: hypertrophic osteoarthropathy, primary, autosomal recessive 1 (PHOAR1) and hypertrophic osteoarthropathy, primary, autosomal recessive 2 (PHOAR2). In this study, we summarized the clinical manifestations and analyzed SLCO2A1 gene in 23 PHOAR2 patients in our center. As a result, 18 patients displayed complete phenotypes of PHO with digital clubbing, periostosis, and pachydermia. 29 mutations were found in total, and 22 of them were novel mutations including 13 missense, three nonsense, four deletion, one frame-shift and one splicing site mutations. Compared with nine PHOAR1 patients we previously reported, PHO patients with SLCO2A1 mutations were all male and presented with a later onset age. Peptic ulcers and myelofibrosis occurred only in PHOAR2 patients. The urinary level of prostaglandin E2 metabolite (PGEM) is significantly higher in PHOAR2 patients than that in PHOAR1 group. In conclusion, this study was the largest cohort to date to summarize PHOAR2 patients and to assess the phenotypic difference between two subtypes of PHO. The difference of urinary PGEM concentration between two subtypes is helpful for the differential diagnosis of PHO., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background/aims: Blood pressure variability (BPV) is a novel cardiovascular risk factor for the population undergoing hemodialysis (HD)., Methods: We conducted a retrospective cohort study of 526 HD patients. Four short-term peridialysis BPV metrics were analyzed: systolic blood pressure (SBP) change, SBP coefficient of variation (CV), SBP intradialytic average real variability (ARV), and absolute SBP residual. Multi variate analysis with Cox regression models were used to account for the potential confounders., Results: Short-term BPV is found to be affected by age, pre-dialysis SBP, antihypertensive drugs, dialysis time, and vascular access. Calcium-channel blockers (CCBs) were found to be associated with lower BPV than those on non-CCB therapy or no antihypertensive drugs. Patients dialyzed in the morning had a greater absolute SBP change than those dialyzed in the afternoon or evening. Patients using fistulas had a lower BPV than catheters. Higher BPV metrics including SBP CV (unadjusted hazard ratio [HR]: 1.37, 95% confidence interval [CI] 1.14-1.66, p=0.001), SBP intradialytic ARV (unadjusted HR: 1.46, 95% CI: 1.20-1.77, p< 0.001), and SBP residual (unadjusted HR: 1.47, 95% CI: 1.21-1.79, p< 0.001) were associated with a greater risk of cardiovascular events. After complete multivariate adjustment for other potential confounders, the HR remained statistically significant for SBP intradialytic ARV (HR 1.31, 95% CI: 1.04-1.66, p=0.024)., Conclusion: Peridialytic BPV may be a potential target for improved blood pressure (BP) management in HD patients. Each short-term BPV metric has different advantages and disadvantages and should be applied according to the clinical context and purpose., (© 2018 The Author(s). Published by S. Karger AG, Basel.)