LncTCONS_00058568 is involved in the pathophysiologic processes mediated by P2X7R in the lower thoracic spinal cord after acute kidney injury.

Acute kidney injury (AKI), a prevalent clinical syndrome, involves the participation of the nervous system in neuroimmune regulation. However, the intricate molecular mechanism that governs renal function regulation by the central nervous system (CNS) is complex and remains incompletely understood. In the present study, we found that the upregulated expression of lncTCONS_00058568 in lower thoracic spinal cord significantly ameliorated AKI-induced renal tissue injury, kidney morphology, inflammation and apoptosis, and suppressed renal sympathetic nerve activity. Mechanistically, the purinergic ionotropic P2X7 receptor (P2X7R) was overexpressed in AKI rats, whereas lncTCONS_00058568 was able to suppress the upregulation of P2X7R. In addition, RNA sequencing data revealed differentially expressed genes associated with nervous system inflammatory responses after lncTCONS_00058568 was overexpressed in AKI rats. Finally, the overexpression of lncTCONS_00058568 inhibited the activation of PI3K/Akt and NF-κB signaling pathways in spinal cord. Taken together, the results from the present study show that lncTCONS_00058568 overexpression prevented renal injury probably by inhibiting sympathetic nerve activity mediated by P2X7R in the lower spinal cord subsequent to I/R-AKI.

USP25 attenuates anti-GBM nephritis in mice by negative feedback regulation of Th17 cell differentiation.

PURPOSE: This study aimed to elucidate the role of USP25 in a mouse model of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). METHODS: USP25-deficient anti-GBM GN mice were generated, and their nephritis progression was monitored. Naïve CD4+ T cells were isolated from spleen lymphocytes and stimulated to differentiate into Th1, Th2, and Th17 cells. This approach was used to investigate the impact of USP25 on CD4+ T lymphocyte differentiation in vitro. Furthermore, changes in USP25 expression were monitored during Th17 differentiation, both in vivo and in vitro. RESULTS: USP25-/- mice with anti-GBM GN exhibited accelerated renal function deterioration, increased infiltration of Th1 and Th17 cells, and elevated RORγt transcription. In vitro experiments demonstrated that USP25-/- CD4+ T lymphocytes had a higher proportion for Th17 cell differentiation and exhibited higher RORγt levels upon stimulation. Wild-type mice with anti-GBM GN showed higher USP25 levels compared to healthy mice, and a positive correlation was observed between USP25 levels and Th17 cell counts. Similar trends were observed in vitro. CONCLUSION: USP25 plays a crucial role in mitigating renal histopathological and functional damage during anti-GBM GN in mice. This protective effect is primarily attributed to USP25's ability to inhibit the differentiation of naïve CD4+ T cells into Th17 cells. The underlying mechanism may involve the downregulation of RORγt. Additionally, during increased inflammatory responses or Th17 cell differentiation, USP25 expression is activated, forming a negative feedback regulatory loop that attenuates immune activation.

Association of metal exposure with arterial stiffness in Chinese adults.

BACKGROUND: Arterial stiffness is an important indicator of cardiovascular aging. However, studies assessing the association between metal exposure and arterial stiffness are limited. OBJECTIVE: The aim of this study was to investigate the independent and joint associations of metal exposure with arterial stiffness. METHODS: This cross-sectional study recruited 2982 Chinese adults from August 2018 to March 2019 in Wuhan, China. The concentrations of 20 urinary metals were determined using inductively coupled plasma mass spectrometer. Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). We used generalized linear model (GLM) to estimate the association of single metal exposure with baPWV. We used weighted quantile sum (WQS) regression to estimate the association of metal mixture with baPWV. RESULTS: In GLM regression analysis, each doubling of urinary copper (Cu) and chromium (Cr) concentrations were associated with 6.48 (95 % CI: 2.51-10.45) cm/s and 3.78 (95 % CI: 0.42-7.14) cm/s increase in baPWV, respectively. In WQS regression analysis, each unit increase in WQS index of the metal mixture was associated with a 9.10 (95 % CI: 2.39-15.82) cm/s increase in baPWV. Cu, Zn, and Cr were the dominant urinary metals associated with baPWV. CONCLUSION: Metal exposure, both individually and in mixture, was associated with an increased risk of arterial stiffness. Our findings may provide a target for preventative strategies against cardiovascular aging.

Exposure to organochlorine pesticides and polychlorinated biphenyls, adherence to an ideal cardiovascular health, and arterial stiffness among Chinese adults.

This study aimed to assess the relationships between exposure to individual organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and their mixture and arterial stiffness and explore whether adherence to an ideal cardiovascular health (CVH) could mitigate these associations. The cross-sectional study enrolled 1437 Chinese adults between March and May 2019 in Wuhan, China. OCPs and PCBs concentrations were measured using solid phase extraction coupled with gas chromatography-tandem mass spectrometry. Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). CVH was determined by three behavioral and four biological metrics and categorized as ideal, intermediate, and poor CVH. We applied generalized linear model and weighted quantile sum (WQS) regression to evaluate the associations of exposure to individual OCPs or PCBs and their mixture with baPWV, respectively. We found that participants with detectable levels of heptachlor epoxide, PCB-153, and PCB-180 had higher baPWV (ß: 34.25, 95% CI 14.28-54.22; ß: 27.64, 95% CI 7.90-47.38; and ß: 30.51, 95% CI 10.68-50.35) than those with undetectable levels. In WQS regression, the mixture of OCPs and PCBs was related to a higher baPWV (ß: 24.93, 95% CI 2.70-47.15). Compared with participants with ideal CVH and undetectable OCPs or PCBs levels, those with poor CVH and detectable OCPs or PCBs levels had the highest increase in baPWV (heptachlor epoxide: ß: 147.94, 95% CI 112.52-183.55; PCB-153: ß: 150.22, 95% CI 115.40-185.04; PCB-180: ß: 147.02, 95% CI 111.66-182.38). Our findings suggested that individual OCPs, PCBs, and their mixture exposure were positively associated with arterial stiffness, and adherence to an ideal CVH may mitigate the adverse effect.

The methyl-CpG-binding domain 2 facilitates pulmonary fibrosis by orchestrating fibroblast to myofibroblast differentiation.

Although DNA methylation has been recognised in the pathogenesis of idiopathic pulmonary fibrosis (IPF), the exact mechanisms are yet to be fully addressed. Herein, we demonstrate that lungs originated from IPF patients and mice after bleomycin (BLM)-induced pulmonary fibrosis are characterised by altered DNA methylation along with overexpression in myofibroblasts of methyl-CpG-binding domain 2 (MBD2), a reader responsible for interpreting DNA methylome-encoded information. Specifically, depletion of Mbd2 in fibroblasts or myofibroblasts protected mice from BLM-induced pulmonary fibrosis coupled with a significant reduction of fibroblast differentiation. Mechanistically, transforming growth factor (TGF)-ß1 induced a positive feedback regulatory loop between TGF-ß receptor I (TßRI), Smad3 and Mbd2, and erythroid differentiation regulator 1 (Erdr1). TGF-ß1 induced fibroblasts to undergo a global DNA hypermethylation along with Mbd2 overexpression in a TßRI/Smad3 dependent manner, and Mbd2 selectively bound to the methylated CpG DNA within the Erdr1 promoter to repress its expression, through which it enhanced TGF-ß/Smad signalling to promote differentiation of fibroblast into myofibroblast and exacerbate pulmonary fibrosis. Therefore, enhancing Erdr1 expression strikingly reversed established pulmonary fibrosis. Collectively, our data support that strategies aimed at silencing Mbd2 or increasing Erdr1 could be viable therapeutic approaches for prevention and treatment of pulmonary fibrosis in clinical settings.

Human epididymis protein 4 aggravates airway inflammation and remodeling in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by chronic inflammation and airway remodeling. Human epididymis protein 4 (HE4) plays a critical role in various inflammatory or fibrotic diseases. However, the role of HE4 in COPD remains unidentified. METHODS: HE4 expression was determined in the lung tissues from COPD patients and cigarette smoke (CS)-exposed mice using immunohistochemical staining, qPCR, or western blot. The plasma level of HE4 was detected by ELISA. The regulations of HE4 in the expressions of CS extract (CSE)-induced inflammatory cytokines in human bronchial epithelial cells (HBE) were investigated through knockdown or overexpression of HE4. The role of secretory HE4 (sHE4) in the differentiation and proliferation in human pulmonary fibroblast cells (HPF) was explored via qPCR, western blot, CCK8 assay or 5-ethynyl-2'-deoxyuridine (EdU) staining. The probe of related mechanism in CSE-induced HE4 increase in HBE was conducted by administrating N-acetylcysteine (NAC). RESULTS: HE4 was up-regulated in both the lung tissue and plasma of COPD patients relative to controls, and the plasma HE4 was negatively associated with lung function in COPD patients. The same enhanced HE4 expression was verified in CS-exposed mice and CSE-induced HBE, but CSE failed to increase HE4 expression in HPF. In vitro experiments showed that reducing HE4 expression in HBE alleviated CSE-induced IL-6 release while overexpressing HE4 facilitated IL-6 expression, mechanistically through affecting phosphorylation of NFκB-p65, whereas intervening HE4 expression had no distinctive influence on IL-8 secretion. Furthermore, we confirmed that sHE4 promoted fibroblast-myofibroblast transition, as indicated by promoting the expression of fibronectin, collagen I and α-SMA via phosphorylation of Smad2. EdU staining and CCK-8 assay demonstrated the pro-proliferative role of sHE4 in HPF, which was further confirmed by enhanced expression of survivin and PCNA. Pretreatment of NAC in CSE or H2O2-induced HBE mitigated HE4 expression. CONCLUSIONS: Our study indicates that HE4 may participate in airway inflammation and remodeling of COPD. Cigarette smoke enhances HE4 expression and secretion in bronchial epithelium mediated by oxidative stress. Increased HE4 promotes IL-6 release in HBE via phosphorylation of NFκB-p65, and sHE4 promotes fibroblastic differentiation and proliferation.

Development and validation of a simplified nomogram predicting individual critical illness of risk in COVID-19: A retrospective study.

This study aims to screen useful predictors of critical cases among coronavirus disease 2019 (COVID-19) patients and to develop a simple-to-use nomogram for clinical utility. A retrospective study was conducted that consisted of a primary cohort with 315 COVID-19 patients and two validation cohorts with 69 and 123 patients, respectively. Logistic regression analyses were used to identify the independent risks of progression to critical. An individualized prediction model was developed, and calibration, decision curve, and clinical impact curves were used to assess the performance of the model. External validations for the predictive nomogram were also provided. The variables of age, comorbid diseases, neutrophil-to-lymphocyte ratio, d-dimer, C-reactive protein, and platelet count were estimated to be independent predictors of progression to critical, which were incorporated to establish a model of the nomogram. It demonstrated good discrimination (with a C-index of 0.923) and calibration. Good discrimination (C-index, 0.882 and 0.906) and calibration were also noted on applying the nomogram in two validation cohorts. The clinical relevance of the nomogram was justified by the decision curve and clinical impact curve analysis. This study presents an individualized prediction nomogram incorporating six clinical characteristics, which can be conveniently applied to assess an individual's risk of progressing to critical COVID-19.

Elevated atherogenic index and higher triglyceride increase risk of kidney function decline: a 7-year cohort study in Chinese adults.

OBJECTIVE: This study explored whether lipid disorders or an elevated atherogenic index of plasma (AIP, a risk factor for cardiovascular diseases) could predict major kidney function decline. METHODS: We conducted a retrospective 7-year cohort study of 3712 Chinese adults followed up between 2010 and 2017. Major kidney function decline was defined as a ≥ 30% reduction in the estimated glomerular filtration rate (eGFR) from baseline. Multivariable logistic regression models were used to evaluate the relationship between lipid profiles and major kidney function decline. Smoking habits, waist circumference, and physical activity were not assessed. RESULTS: During the 7-year follow-up, 1.70% (n = 63) of the participants developed major kidney function decline. After adjustment for potential confounders, the odds ratios (ORs) for developing eGFR decline with per standard deviation increase were 1.23 [95% confidence interval (CI): 1.06-1.43] for triglyceride and 2.55 (95% CI: 1.01-6.42) for AIP in all participants. Furthermore, in the stratified analysis, we found sex-related differences; triglyceride and AIP were only independently associated with the risk of eGFR decline in men (OR, 1.27, 95% CI: 1.08-1.48; OR, 3.98, 95% CI: 1.22-12.99, respectively). When the participants were divided into groups according to the baseline lipid status, association was observed only between abnormal AIP and eGFR decline (all p values < 0.05). CONCLUSION: Our findings suggest that a higher serum triglyceride level or an elevated AIP increases the risk of major kidney function decline in Chinese men with normal kidney function. Thus, assessment of AIP may help identify the risk of eGFR decline.

The Plasma Soluble Urokinase Plasminogen Activator Receptor Is Related to Disease Activity of Patients with ANCA-Associated Vasculitis.

OBJECTIVE: The soluble urokinase plasminogen activator receptor (suPAR) is associated with kidney diseases and is used as a prognostic factor of renal function progression. The aim of this study was to explore whether circulating suPAR was associated with antineutrophil cytoplasmic autoantibody- (ANCA-) associated vasculitis (AAV) disease activity. METHODS: We evaluated 90 AAV patients with follow-up data and 35 normal controls; their plasma suPAR and C-reactive protein (CRP) levels were measured by ELISA. Associations between these levels, clinical parameters, and prognosis were analyzed. RESULTS: Plasma suPAR levels in AAV patients were significantly higher than in healthy controls (5,920.08 ± 3,447.17 vs. 1,441.97 ± 835.04 pg/mL, P < 0.001). Furthermore, suPAR was significantly elevated in AAV patients in active stage compared to those in partial remissions (6,492.19 ± 3,689.48 vs. 5,031.86 ± 2,489.01 pg/mL, P = 0.039). Correlation analyses demonstrated that suPAR levels positively correlated with initial serum creatinine, BVAS, CRP, and procalcitonin concentration, and negatively correlated with eGFR and C3 circulating levels. In a Kaplan-Meier survival analysis, patients with plasma suPAR levels >5683.3 pg/mL showed poorer survival than patients with lower levels (log-rank, P = 0.001). Besides, multivariate analyses confirmed that plasma suPAR levels were an independent adverse prognostic factor for a composite outcome of end-stage renal disease (ESRD) or death, after adjusting for age and gender (HR 1.05, 95% CI = 1.01 - 1.11, P = 0.043). Receiver operating characteristic curves showed a suPAR cutoff value >6662.2 pg/mL for composite outcome with 68% sensitivity and 88% specificity, with an AUC = 0.82, (95% CI = 0.68 - 0.96, P < 0.001). CONCLUSION: Circulating suPAR levels might be a marker of activity correlated with disease activity in AAV patients, and, to some extent, could be a factor of poor prognosis.

GDF11 impairs liver regeneration in mice after partial hepatectomy.

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor (TGF)-ß superfamily. The rejuvenative effect of GDF11 has been called into question recently, and its role in liver regeneration is unclear. Here, we investigated the pathophysiologic role of GDF11, as well as its plausible signaling mechanisms in a mouse model of partial hepatectomy (PH). We demonstrated that both serum and hepatic GDF11 protein expression increased following PH. Treatment with adeno-associated viruses-GDF11 and recombinant GDF11 protein severely impaired liver regeneration, whereas inhibition of GDF11 activity with neutralizing antibodies significantly improved liver regeneration after PH. In vitro, GDF11 treatment significantly delayed cell proliferation and induced cell-cycle arrest in α mouse liver 12 (AML12) cells. Moreover, GDF11 activated TGF-ß-SMAD2/3 signaling pathway. Inhibition of GDF11-induced SMAD2/3 activity significantly blocked GDF11-mediated reduction in cell proliferation both in vivo and in vitro. In the clinical setting, GDF11 levels were significantly elevated in patients after hepatectomy. Collectively, these results indicate that rather than a 'rejuvenating' agent, GDF11 impairs liver regeneration after PH. Suppression of cell-cycle progression via TGF-ß-SMAD2/3 signaling pathway may be a key mechanism by which GDF11 inhibits liver regeneration.

Thyroid function, body mass index, and metabolic risk markers in euthyroid adults: a cohort study.

BACKGROUND: In recent years, the relationship between thyroid stimulating hormone (TSH) and obesity has been widely discussed. However, it is unclear how thyroid hormone concentrations relate to body weight and its impact on metabolic risk markers. This study aimed to assess how thyroid function is linked to underweight, overweight, or obesity, and metabolic risk markers in adults. METHODS: A total of 16,975 subjects, aged 18-80 years, who attended the Health Management Center of Tongji Hospital, Wuhan, China were enrolled in this study. Anthropometric and laboratory data were collected and analyzed. RESULTS: Serum free triiodothyronine (fT3) and fT3/free thyroxine (fT4) ratio (fT3/fT4) were positively associated with body mass index (BMI) (P < 0.001), while there was a negative relationship between fT4 and BMI (P < 0.001) according to multivariable regression analysis adjusted for age and sex. Associations between thyroid hormone concentrations and markers of blood pressure, and lipid and glucose metabolism were identified after adjustment for age, sex, and BMI, with TSH being negatively associated with fasting blood glucose (FBG). fT3 was positively associated with systolic blood pressure and low-density lipoprotein-cholesterol, while fT4 was positively associated with diastolic blood pressure, FBG, and high-density lipoprotein-cholesterol (HDL-C), and negatively associated with hemoglobin A1c (HbA1c) and triglyceride. Finally, fT3/fT4 was positively associated with HbA1c and triglyceride, and negatively associated with HDL-C. CONCLUSIONS: Overweight or obese participants had a high serum concentration of fT3, high fT3/fT4 ratio, and a low concentration of fT4. Underweight participants had high concentrations of fT4 and low concentrations of fT3. Thus, relationships between thyroid hormones and metabolic risk markers were identified which suggest that thyroid function might be one factor that influences body weight and the co-morbidities of obesity.

Role of capsaicin sensitive sensory nerves in ischemia reperfusion-induced acute kidney injury in rats.

Acute kidney injury (AKI) is a common kidney disorder which is associated with a high risk of mortality. Extensive evidence revealed the participation of renal afferent sensory nerves in the pathophysiology of renal ischemia reperfusion (IR) injury, however the role of these nerves in renal IR injury is controversial and remains to be further explored. Here, we report that capsaicin sensitive sensory nerves and neuropeptides prevented renal damage in AKI induced by IR injury. The sensory afferent degeneration model was established by injecting 50 mg/kg of capsaicin to male neonatal rats and verified by the tail flick test and reduced sensory neuropeptide of substance P and calcitonin gene related peptide in spinal cord, dorsal root ganglion and kidney after 12 weeks. Then, a model of renal IR injury was established. The sensory afferent degeneration in the AKI group increased the level of serum creatinine, NGAL and KIM-1, aggravated to some extent renal pathological damage, and enhanced the proinflammatory cytokines expressions and tubular cell apoptosis. In addition, it was also discovered that the level of phospho-ERK/ERK (p-ERK/ERK) showed an increase in spinal cord and kidney after degeneration of capsaicin sensitive sensory nerves. In conclusion, the degeneration of sensory nerves aggravated IR-induced AKI in rats, and the activated ERK signaling in spinal cord and kidney after sensory afferent degeneration might be the possible mechanism in the aggravated renal injury.

Epidemiology and risk factors in CKD patients with pulmonary hypertension: a retrospective study.

BACKGROUND: Pulmonary hypertension (PH) is a rare disease often associated with high mortality and is recently recognized as a common complication secondary to chronic kidney disease (CKD). Epidemiological data for this disorder across the spectrum of CKD is poorly understood. METHODS: We retrospectively analyzed 705 CKD patients with complete clinical records from July 2013 to September 2015. All the patients were estimated by echocardiography and PH was defined as pulmonary artery systolic pressure (PASP) > 35 mmHg. The prevalence of PH in CKD patients was investigated, and their association was evaluated with a logistic regression model. RESULTS: The overall prevalence of PH was 47.38%, in which mild, moderate and severe PH accounted for 22.13, 15.04 and 10.21%, respectively. The prevalence of PH in CKD stage 1-5 was 14.29, 33.33, 38.89, 40.91 and 64.47%. The prevalence of total PH was 57.63% in PD patients and 58.82% in HD patients. Compared with the non-dialysis patients, the prevalence of PH was much higher in patients receiving dialysis. Body mass index (BMI), hemoglobin, triglyceride (TG), proteinuria, parathyroid hormone (PTH) and estimated glomerular filtration rate (eGFR) were independent risk factors of PH in CKD patients. CONCLUSIONS: The prevalence of PH is increased with the deterioration of renal function, however, which has no direct relation to the severity of PH. PH occurs more frequently in dialysis patients. Higher BMI and TG, more sever anemia, proteinuria and secondary hyperparathyroidism, poor renal dysfunction predict predict the more prevalence of PH in CKD patients.

Analysis of 4931 renal biopsy data in central China from 1994 to 2014.

The purpose of this study is to investigate the changing spectrum and clinicopathologic correlation of biopsy-proven renal diseases in central China. We retrospectively analyzed data of 4931 patients who underwent renal biopsy in ten hospitals between September 1994 and December 2014. Among them, 81.55% were primary glomerular diseases (GD), and 13.02% were secondary GD. IgA nephropathy (IgAN) was the most common primary GD (43.45%), followed by focal glomerulonephritis (16.79%), mesangial proliferative glomerulonephritis (MsPGN, 14.35%), and membranous nephropathy (MN, 13.28%). IgAN was leading primary GD in patients under 60 years old, while MN was the leading one over 60 years old. The most frequent secondary GD was lupus nephritis (LN) (47.35%). The prevalence of IgAN, MN and minimal change disease was found to increase significantly (p < 0.001, p < 0.001, and p < 0.01, respectively), while that of MsPGN, membranoproliferative glomerulonephritis and LN decreased significantly (p < 0.001, p < 0.001, and p < 0.05, respectively). The main indication for renal biopsy was proteinuria and hematuria (49.03%), followed by nephrotic syndrome (NS, 20.36%). IgAN was the most common cause in patients with proteinuria and hematuria, chronic-progressive kidney injury, hematuria and acute kidney injury; and MN was the leading cause of NS. Primary GD remained the predominant renal disease in central China. IgAN and LN were the most prevalent histopathologic lesions of primary and secondary GD, respectively. The spectrum of biopsy-proven renal disease had a great change in the past two decades. Proteinuria and hematuria was the main indication for renal biopsy.

Galectin-9 ameliorates anti-GBM glomerulonephritis by inhibiting Th1 and Th17 immune responses in mice.

Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a Th1- and Th17-predominant autoimmune disease. Galectin-9 (Gal-9), identified as the ligand of Tim-3, functions in diverse biological processes and leads to the apoptosis of CD4(+)Tim-3(+) T cells. It is still unclear how Gal-9 regulates the functions of Th1 and Th17 cells and prevents renal injury in anti-GBM GN. In this study, Gal-9 was administered to anti-GBM GN mice for 7 days. We found that Gal-9 retarded the increase of Scr, ameliorated renal tubular injury, and reduced the formation of crescents. The infiltration of Th1 and Th17 cells into the spleen and kidneys significantly decreased in Gal-9-treated nephritic mice. The reduced infiltration of Th1 and Th17 cells might be associated with the downregulation of CCL-20, CXCL-9, and CXCL-10 mRNAs in the kidney. In parallel, the blood levels of IFN-γ and IL-17A declined in Gal-9-treated nephritic mice at days 21 and 28. In addition, an enhanced Th2 cell-mediated immune response was observed in the kidneys of nephritic mice after a 7-day injection of Gal-9. In conclusion, the protective role of Gal-9 in anti-GBM GN is associated with the inhibition of Th1 and Th17 cell-mediated immune responses and enhanced Th2 immunity in the kidney.

Effect of uric-acid-lowering therapy on progression of chronic kidney disease: a meta-analysis.

The efficacy and safety of uric-acid-lowering therapy (UALT) on slowing the progression of chronic kidney disease (CKD) accompanied by hyperuricemia were assessed. We searched Cochrane Library, PubMed, EMbase, CNKI, Wanfang and Vip databases up to November 15, 2012 for randomized controlled trials (RCTs) which compared the effect of UALT to control therapy in hyperuricemic patients secondary to CKD, and then performed quality evaluation and meta-analysis on the included studies. Seven RCTs involving 451 cases were included. UALT delayed the increase of serum creatinine (MD=-62.55 µmol/L, 95% CI: -98.10 to -26.99) and blood urea nitrogen (MD= -6.15 mmol/L, 95% CI: -8.17 to -4.13) as well as the decrease of glomerular filtration rate [MD=5.65 mL/(min·1.73 m2), 95% CI: 1.88 to 9.41], decreased systolic blood pressure (SBP) (MD= -6.08 mmHg, 95% CI: -11.67 to -0.49), and reduced the risk of the renal disease progression (RR=0.30, 95% CI: 0.19 to 0.46). However, there was no statistically significant difference in 24-h urinary protein quantity and diastolic blood pressure (P>0.05). We identified that UALT could delay the progression of CKD with secondary hyperuricemia. And this also indirectly proved that hyperuricemia was a risk factor for the CKD progression.

Individual and joint effects of organophosphate esters and hypertension or diabetes on renal injury among Chinese adults.

Exposure to environmental contaminants and the development of hypertension and diabetes represent crucial risk factors for chronic kidney disease (CKD). Toxicological studies have revealed that organophosphate esters (OPEs) impair kidney function. However, the joint effects of OPE exposure on kidney injury and the interactions of OPE exposure with hypertension or diabetes on kidney injury remain unclear. Our study aimed to investigate the individual and joint effects of OPE exposure on renal injury, as well as the potential interaction between OPE exposure and hypertension or diabetes on kidney injury. The study enrolled 1938 participants from Wuhan, China. To explore the relationship between OPE exposure and renal injury, we conducted multivariate linear and logistic regression analysis. The results indicated that each unit increase in 4-hydroxyphenyl diphenyl phosphate (4-HO-DPHP), bis(2-butoxyethyl) phosphate (BBOEP), and tris(2-chloroethyl) phosphate (TCEP) (1 µg/L-ln transformed) was associated with a decreased 0.57 mL/min/1.73 m2 (95%CI: -1.05, -0.09), 0.85 mL/min/1.73 m2 (95%CI: -1.52, -0.19) and 1.24 mL/min/1.73 m2 (95%CI: -2.26, -0.23) of estimated glomerular filtration rate (eGFR), while each unit increase in 4-HO-DPHP and BBOEP (1 µg/L-ln transformed) was associated with 14% and 20% elevation of incident impaired renal function (IRF) risk. Notably the highest tertile of BCIPHIPP was positively associated with eGFR, although the p for trend ＞ 0.05. We employed Bayesian kernel machine regression (BKMR) and quartile-based g-computation (qgcomp) models to explore the joint effects of OPE mixtures on eGFR and IRF. Both the results of BKMR and qgcomp model consistently demonstrated negative associations between OPE mixtures and eGFR, and TCEP and 4-HO-DPHP were major contributors. Furthermore, we observed multiplicative interactions of diphenyl phosphate (DPHP), BBOEP, di-ocresyl phosphate (DoCP) & di-p-cresyl phosphate (DpCP), 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) and hypertension or diabetes on kidney injury (all P＜0.05). Those with diabetes or hypertension and higher OPE metabolite concentrations had increased risk of kidney function impairment compared to those who did not have diabetes or hypertension. These findings suggest that specific OPE exposure may elevate the risk of renal injury, particularly among hypertensive and diabetic populations.

Association between essential metals, adherence to healthy lifestyle behavior, and ankle-brachial index.

BACKGROUND: Ankle-brachial index (ABI) is a noninvasive diagnostic method for peripheral arterial disease (PAD) and a predictor of cardiovascular events. OBJECTIVE: The present study aimed to evaluate the association between individual or combined essential metals and ABI, as well as assess the collective impact of essential metals when coupled with healthy lifestyle on ABI. METHODS: A total of 2865 participants were recruited in Wuhan Tongji Hospital between August 2018 and March 2019. Concentrations of essential metals in urine were measured by inductively coupled plasma mass spectrometer. RESULTS: The results of general linear regression models demonstrated that after adjusting for confounding factors, there was a positive association between ABI increase and per unit increase of log 10-transformed, creatinine-corrected urinary Cr (ß (95 % CI): 0.010 (0.004, 0.016), PFDR = 0.007), Fe (ß (95 % CI): 0.010 (0.003, 0.017), PFDR = 0.018), and Co (ß (95 % CI): 0.013 (0.005, 0.021), PFDR = 0.007). The WQS regression revealed a positive relationship between the mixture of essential metals and ABI (ß (95 % CI): 0.006 (0.003, 0.010), P < 0.001), with Cr and Co contributing most to the relationship (weighted 45.48 % and 40.14 %, respectively). Compared to individuals with unfavorable lifestyle and the lowest quartile of Cr, Fe and Co, those with favorable lifestyle and the highest quartile of Cr, Fe and Co exhibited the most increase in ABI (ß (95 % CI): 0.030 (0.017, 0.044) for Cr, ß (95 % CI): 0.027 (0.013, 0.040) for Fe, and ß (95 % CI): 0.030 (0.016, 0.044) for Co). CONCLUSION: In summary, our study indicates that adequate essential metal intake together with healthy lifestyle behaviors perform crucial roles in PAD protection.

The association of organochlorine pesticides and polychlorinated biphenyls exposure with dyslipidemia and blood lipids: The mediating effect of white blood cell counts.

Epidemiological evidence regarding the associations of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) with lipid metabolism and its potential biological mechanisms remain largely unknown. We intended to explore the associations of OCPs and PCBs with dyslipidemia and blood lipid levels, and further evaluate the mediating role of total and differential white blood cell (WBC) counts. We measured the blood lipid levels, the concentration of OCPs/PCBs and WBC counts in serum among 2036 adults in Wuhan city, China. In the multiple-pollutant models, the results showed that ß-hexachlorocyclohexane (HCH), p,p'-dichlorodiphenyldichloroethylene (DDE), and PCB-153 were positively correlated with increased odds of dyslipidemia. p,p'-DDE and PCB-153 were correlated with elevated triglyceride (TG) and lowered high-density lipoprotein cholesterol (HDL-c). A positive relationship was observed between p,p'-DDE and total cholesterol (TC) as well. Meanwhile, weighted quantile sum (WQS) regression analyses revealed that PCB and OCP mixtures were positively related to dyslipidemia risk and TG and negatively associated with HDL-c, to which p,p'-DDE was the major contributor. BMI, gender and age might modify the associations of OCPs and PCBs with dyslipidemia and TG. Furthermore, we found that WBC counts were significantly associated with dyslipidemia and blood lipid levels, and a positive correlation was also found between p,p'-DDE and lymphocyte count. Mediation analysis further indicated that lymphocyte count might mediate the associations of p,p'-DDE with dyslipidemia, TG, and TC. Accordingly, our results showed that OCPs and PCBs were related to abnormal lipid metabolism, which was partially mediated by WBC counts.

Association between organophosphate esters individual and mixed exposure with the risk of hyperlipidemia and serum lipid levels among adults in Wuhan, China.

Toxicologic studies reported that organophosphate esters (OPEs) may disrupt lipid metabolism, thus affecting serum lipid levels. However, epidemiological evidence regarding the association between OPEs and the risk of hyperlipidemia (HPL) as well as serum lipid levels is scarce. In the present study, our aim was to investigate the impact of individual and mixed OPE exposure on HPL. A total of 1981 Chinese adults were involved based on a cross-sectional design. Overall, we found a positive association between bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and the risk of HPL. Bis(1-chloro-2-propyl) phosphate (BCIPHIPP) showed a positive association with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). BDCIPP, diphenyl phosphate (DPHP), di-ocresyl phosphate and di-p-cresyl phosphate (Docp&Dpcp), and 4-hydroxyphenyl-diphenyl phosphate (4-OH-DPHP) exhibited a negative association with high-density lipoprotein cholesterol (HDL-C). In stratified analyses, BDCIPP and BCIPHIPP were significantly correlated with the increased risk of HPL in the age ≤ 45 group. Bis(2-butoxyethyl) phosphate (BBOEP) was in relationship with an elevated risk of HPL in the subgroup of BMI < 24 kg/m2. BDCIPP was also positively associated with HPL in men. Quantile-based g computation (qgcomp) and generalized weighted quantile sum regression (gWQS) models demonstrated a negative association between OPEs mixed exposure and HDL-c in the total population, as well as a positive effect of them on HPL in the subgroup of age ≤ 45 years, which is consistent with the individual analyses. Furthermore, joint effect analyses revealed that participants with detected BDCIPP urinary levels and unhealthy lifestyles had the highest risk of HPL. Our findings offer evidence supporting the correlation between exposure to OPE and the risk of HPL, necessitating further prospective studies for validation.