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BackgroundBoth diabetic kidney disease (DKD) and chronic kidney disease (CKD) are more prevalent among individuals with lower levels of education in observational studies. To quantify the mediation effect of recognized cardiometabolic traits, we obtain causal estimates between education and DKD as well as CKD.Materials and methodsWe assessed the causal effect of education on DKD and CKD, separately estimated the causal effect of 26 cardiometabolic traits on DKD and CKD, and finally calculated the mediating effects and mediating proportions of each using two-step, two-sample multivariable Mendelian randomization (MVMR). Furthermore, the genetic association between exposure, mediators, and outcomes was investigated using linkage disequilibrium score (LDSC) regression analysis. Expression quantitative trait loci (eQTL) were retrieved from the Genotype-Tissue Expression Project (GTEx) v8 to serve as genetic instrumental variables. Transcriptome-wide association studies (TWAS), Bayesian colocalization analysis, and Summary-data-based Mendelian Randomization (SMR) analysis were performed to explore underlying susceptibility genes between education, mediators, and kidney diseases.ResultsHigher education with a genetically predicted 1-SD (4.2 years) was linked to a 48.64% decreased risk of DKD and a 29.08% decreased risk of CKD. After extensive evaluation of 26 cardiometabolic traits, 7 and 6 causal mediators were identified as mediating the effects of education on DKD and CKD, respectively. The largest mediating factor between education and DKD was BMI, which was followed by WHR, T2D, fasting insulin, SBP, fasting glucose, and DBP. In contrast, candidate mediators in the education-to-CKD pathway included BMI, followed by cigarettes smoked per day, WHR, SBP, T2D, and DBP. MR analysis revealed that TP53INP1 was found to be a shared susceptibility gene for cardiometabolic traits and DKD, while L3MBTL3 was found to be a shared susceptibility gene for cardiometabolic traits and CKD.ConclusionOur findings provide solid evidence that education has a causally protective effect on the development of DKD and CKD. We additionally reveal significant directions for intervention on cardiometabolic traits that mitigate the negative effects of educational inequities on the onset of DKD and CKD. Our work demonstrates a shared genetic basis between education, cardiometabolic traits, and kidney diseases. Future research aiming at lowering kidney risk may benefit from these findings.

Abstract IgG4-related disease (IgG4-RD) has complex clinical manifestations ranging from fibrosis and inflammation to deregulated metabolism. The molecular mechanisms underpinning these phenotypes are unclear. In this study, by using IgG4-RD patient peripheral blood mononuclear cells (PBMCs), IgG4-RD cell lines and Usp25 knockout mice, we show that ubiquitin-specific protease 25 (USP25) engages in multiple pathways to regulate fibrotic and inflammatory pathways that are characteristic to IgG4-RD. Reduced USP25 expression in IgG4-RD leads to increased SMAD3 activation, which contributes to fibrosis and induces inflammation through the IL-1β inflammatory axis. Mechanistically, USP25 prevents ubiquitination of RAC1, thus, downregulation of USP25 leads to ubiquitination and degradation of RAC1. Decreased RAC1 levels result in reduced aldolase A release from the actin cytoskeleton, which then lowers glycolysis. The expression of LYN, a component of the B cell receptor signalosome is also reduced in USP25-deficient B cells, which might result in B cell activation deficiency. Altogether, our results indicate a potential anti-inflammatory and anti-fibrotic role for USP25 and make USP25 a promising diagnostic marker and potential therapeutic target in IgG4-RD.

ABSTRACT: Black soldier fly (BSF) larvae convert wastes into protein, playing a vital role in addressing the challenge of sustainable poultry production. These larvae accumulate toxic substances, posing a risk to feed and food safety. This study investigates the effects of substituting soybean meal with different levels of BSF larvae meal on laying performance, egg quality, serum analysis, and the deposition of various metals in eggs, meat, and excreta. A total of 1,008 Lohmann hens (age 48 wk) were randomly assigned to 4 treatments. The treatments consisted of corn-soybean meal (CK) diet replaced with 7% (BSF7), 14% (BSF14), and 21% (BSF21) BSF larvae meal. Each treatment consisted of 6 replicates with 42 hens each and the trial lasted for 8 wk. Dietary BSF larvae meal treatments increased (linear, P < 0.05) the laying rate (1.52 to 1.95%) and decreased (linear, P < 0.01) the feed intake (3.64–3.86 g) during the entire experiment. During 48 to 52 wk, egg weight was decreased (P < 0.001) 0.93 g for the BSF21 group compared to CK group, however, during 52-56 wk, no differences in egg weight were observed among treatments. The addition of BSF larvae meal enhanced the eggshell strength (linear, P < 0.05), with no effect on the albumen height and yolk weight (P > 0.05). Low transfer of arsenic, lead, and cadmium concentration was observed in the egg yolk and egg white across different treatments (P > 0.05). Conversely, the concentrations of these metals and iron showed an increase, while Zinc exhibited a decrease in excreta as the dietary intake of BSF larvae meal increased. The chromium and iron increased linearly (P < 0.001) in the egg white with the inclusion of BSF larvae meal. Egg white iron and chromium showed a strong positive correlation with the dietary zinc and copper. Taken together, BSF larvae can replace soybean meal completely in laying diet, however, careful attention requires to elevated metal levels in diet and excreta.

Background Previous observational studies have shown that immune cells play an important role in IgA nephropathy. However, the specific causal relationship between the two is inconsistent.Methods We used a two-sample mendelian randomization(MR) analysis to investigate the causal association between 731 immune cell signatures and IgA nephropathy in this study. Based on published GWAS data, immune cells were characterized by four immune types absolute cell (AC) counts, median fluorescence intensity (MFI), morphological parameters (MP), relative cell (RC) counts. Meanwhile, heterogeneity test, horizontal pleiotropy and sensitivity test were used to evaluate the robustness and reliability of the results.Results An important causal association was achieved for 14 RC traits/IgA nephropathy, 3 AC traits/IgA nephropathy, 10 MFI traits/IgA nephropathy, and 1 MP trait/IgA nephropathy. However, after false discovery rate (FDR) correction, only one immunophenotype was found to be protective against IgA nephropathy. The OR of herpesvirus entry mediator (HVEM) on terminally differentiated CD4+ T cell (maturation stages of T-cell panel) on IgA nephropathy risk was estimated to be 0.727 (95%CI: 0.624-0.847, p = 4.20e − 05, PFDR = 0.023) according to inverse variance weighting (IVW) method, and the weighted-median method yielded similar results (OR = 0.743, 95% CI: 0.596-0.927, p = 0.008). Although not statistically significant, the association was consistent with MR-Egger, simple mode and weighted mode.Conclusions Our study further confirmed that immune cells play a complex and important role in the pathogenesis of IgA nephropathy, providing evidence for clinical research.

Diabetic kidney disease (DKD) is one of the major causes of end-stage renal disease and one of the significant complications of diabetes. This study aims to identify the main differentially expressed genes in DKD from transcriptome sequencing results and analyze their diagnostic value. The present study sequenced db/m mouse and db/db mouse to determine the ALOX12 genetic changes related to DKD. After preliminary validation, ALOX12 levels were significantly elevated in the blood of DKD patients, but not during disease progression. Moreover, urine ALOX12 was increased only in macroalbuminuria patients. Therefore, to visualize the diagnostic efficacy of ALOX12 on the onset and progression of renal injury in DKD, we collected kidney tissue from patients for immunohistochemical staining. ALOX12 was increased in the kidneys of patients with DKD and was more elevated in macroalbuminuria patients. Clinical chemical and pathological data analysis indicated a correlation between ALOX12 protein expression and renal tubule injury. Further immunofluorescence double staining showed that ALOX12 was expressed in both proximal tubules and distal tubules. Finally, the diagnostic value of the identified gene in the progression of DKD was assessed using receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) value for ALOX12 in the diagnosis of DKD entering the macroalbuminuria stage was 0.736, suggesting that ALOX12 has good diagnostic efficacy. During the development of DKD, the expression levels of ALOX12 in renal tubules were significantly increased and can be used as one of the predictors of the progression to macroalbuminuria in patients with DKD.

Trichloroethylene (TCE), a widely distributed environmental chemical contaminant, is extensively dispersed throughout the environment. Individuals who are exposed to TCE may manifest occupational medicamentose-like dermatitis due to trichloroethylene (OMDT). Renal impairment typically manifests in the initial phase of OMDT and is intricately linked to the disease progression and patient outcomes. Although recombinant human tumor necrosis factor-α receptor II fusion protein (rh TNFR:Fc) has been employed in the clinical management of OMDT, there was no substantial improvement in renal function observed in patients following one week of treatment. This study primarily examined the mechanism of TNFα- and IFNγ-induced endothelial cells (ECs) PANoptosis in TCE-induced kidney injury and hypothesized that the synergistic effect of TNFα and IFNγ could be the key factor affecting the efficacy of rh TNFR:Fc therapy in OMDT patients. A TCE-sensitized mouse model was utilized in this study to investigate the effects of TNFα and IFNγ neutralizing antibodies on renal vascular endothelial cell PANoptosis. The gene of interferon regulatory factor 1 (IRF1) in human umbilical vein endothelial cells (HUVEC) was silenced by using small interfering RNA (siRNA), and the cells were then treated with TNFα and IFNγ recombinant protein to investigate the mechanism of TNFα combined with IFNγ-induced PANoptosis in HUVEC. The findings indicated that mice sensitized to TCE exhibited increased levels of PANoptosis-related markers in renal endothelial cells, and treatment with TNFα and IFNγ neutralizing antibodies resulted in a significant reduction in PANoptosis and improvement in renal function. In vitro experiments demonstrated that silencing IRF1 could reverse TNFα and IFNγ-induced PANoptosis in endothelial cells. These results suggest that the efficacy of rh TNFR:Fc may be influenced by TNFα and IFNγ-mediated PANoptosis in kidney vascular endothelial cells. The joint application of TNFα and IFNγ neutralizing antibody represented a solid alternative to existing therapeutics.

Abstract Background Growing evidence has demonstrated that patients undergoing peritoneal dialysis (PD) are more likely to experience cognitive impairment than patients with non-dialysis end-stage renal disease (ESRD); however, the underlying mechanisms remain unclear. This study aimed to identify the role and predictive significance of gut microbiome alterations in PD-associated cognitive impairment. Methods A total of 29 non-dialysis ESRD patients and 28 PD patients were enrolled in this study and divided into subgroups according to the Montreal Cognitive Assessment (MoCA). Faecal samples were analyzed using 16 S rRNA. Mini-Mental State Examination (MMSE) and MoCA scores were used to assess the degree of cognitive impairment in patients. Results The 16 S rRNA analysis demonstrated differences in gut microbiome abundance and structure between PD and non-dialysis ESRD patients and between PD patients with cognitive impairment (PCI) and PD patients with normal cognition (PNCI). At family and genus levels, Prevotellaceae exhibited the greatest structure difference, while Lactobacillus exhibited the greatest abundance difference between PCI and PNCI. Altered microbiota abundance significantly correlated with cognitive function and serum indicators in PD. In addition, different modules related to fatty acid, lipid, pantothenate, and coenzyme A biosynthesis, and tyrosine and tryptophan metabolism were inferred from 16 S rRNA data between PCI and PNCI. Both groups could be distinguished using models based on the abundance of Lactobacillaceae (Area under curve [AUC] = 0.83), Actinomycetaceae (AUC = 0.798), and Prevotellaceae (AUC = 0.778) families and Lactobacillus (AUC = 0.848) and Actinomyces (AUC = 0.798) genera. Conclusion Gut microbiome evaluation could aid early cognitive impairment diagnosis in patients undergoing PD.

Macrophytes are crucial in maintaining the equilibrium of aquatic ecosystems. However, the pattern of macrophyte-derived caffeic acid (CA) release under heavy metal stress is yet to be fully understood. More importantly, due to its functional groups, CA may be a precursor to the formation of disinfection by-products, posing threats to water ecology and even safety of human drinking water. This study analyzed the responses of CA released by Vallisneria natans (V. natans) and Pistia stratiotes (P. Stratiotes) when exposed to Cu2+ and Mn2+ stress. Additionally, the CA levels in two constructed wetland ponds were detected and the degradation kinetics of CA during chlorination were investigated. Results indicated that CA occurred in two constructed wetland ponds with the concentrations of 44.727 μg/L (planted with V. natans) and 61.607 μg/L (planted with P. Stratiotes). Notably, heavy metal stress could significantly affect CA release from V. natans and P. Stratiotes. In general, under Cu2+ stress, V. natans secreted far more CA than under Mn2+ stress, the level could reach up to 435.303 μg/L. However, compared to V. natans, P. Stratiotes was less affected by Cu2+ and Mn2+ stress, releasing a maximum CA content of 55.582 μg/L under 5 mg/L Mn2+ stress. Aquatic macrophytes secreted more CA in response to heavy metal stresses and protected macrophytes from harmful heavy metals. CA degradation followed the pseudo first-order kinetics model, and the chlorination of CA conformed to a second-order reaction. The reaction rate significantly accelerated as NaClO, pH, temperature and Br- concentration increased. A new pathway for CA degradation and a new DBP 2, 2, 3, 3-tetrachloropropanal were observed. These findings pointed at a new direction into the adverse effect of CA, potentially paving the way for new strategies to solve drinking water safety problems.

We investigated the effects of ultrasound-assisted ethylenediaminetetraacetic acid (EDTA) and citric acid (CA) washing on heavy metal (HM) removal, residual HM mobility, and sewage sludge quality. EDTA and CA washing of sewage sludge successfully reduced the total concentration of HMs after one round of washing, but the mobility of residual HMs increased significantly. The eluate had a high concentration of HMs and nutrients (nitrogen, phosphorus, potassium, and total organic carbon), although the nutritional content of the sludge remained high. The three-phase ratio of the sludge after six rounds of washing by CA was closest to the ideal three-phase ratio, and the degree of influence on the physical structure of the soil after a land application was reduced, according to the fluctuation of generalized soil structure index (GSSI) and soil three-phase structure distance (STPSD) values. The results indicate that CA as an environmental-friendly washing agent can be the superior choice for sludge HM washing; single washing of sewage sludge may increase the mobility of residual HMs, so multiple washings should be considered for land application of sludge. HIGHLIGHTS Ultrasound-assisted chemical washing is a useful and efficient solution to remove HMs from sewage sludge.; The higher concentration (≥0.4 M) of biodegradable CA eluent could effectively reduce HMs in the sewage sludge compared to the traditional non-biodegradable EDTA eluent.;

The geological conditions evaluation of coalbed methane (CBM) is of great significance to CBM exploration and development. The CBM resources in the Southern Sichuan Coalfield (SSC) of China are very abundant; however, the CBM investigation works in this area are only just beginning, and the basic geological research of CBM is seriously inadequate, restricting CBM exploration and development. Therefore, in this study, a representative CBM block (Dacun) in the SSC was selected, and the CBM geological conditions were evaluated based on field injection/fall-off well testing, gas content and composition measurements, and a series of laboratory experiments. The results show that the CH4 concentrations of coal seams in the Dacun Block, overall, take on an increasing trend as the depth increases, and the CH4 weathering zone depth is 310 m. Due to the coupled control of temperature and formation pressure, the gas content shows a “increase→decrease” trend as the depth increases, and the critical depth is around 700 m. The CBM is enriched in the hinge zone of the Dacun syncline. The moisture content shows a negative correlation with CBM gas content. The porosities of coal seams vary from 4.20% to 5.41% and increase with the Ro,max. The permeabilities of coal seams show a strong heterogeneity with values ranging from 0.001mD to 2.85 mD and present a decreasing trend with the increase in depth. Moreover, a negative relationship exists between coal permeability and minimum horizontal stress magnitude. The reservoir pressure coefficients are between 0.51 and 1.26 and show a fluctuation change trend (increase→decrease→increase) as the depth increases, reflecting that three sets of independent superposed gas-bearing systems possibly exist vertically in the Longtan Formation of the study area. The Langmuir volumes (VL) of coals range from 22.67 to 36.84 m3/t, indicating the coals have strong adsorptivity. The VL presents a parabolic change of first increasing and then decreasing with the increase in depth, and the turning depth is around 700 m, consistent with the critical depth of gas content. The gas saturations of coal seams are, overall, low, with values varying from 29.10% to 116.48% (avg. 68.45%). Both gas content and reservoir pressure show a positive correlation with gas saturation. The CBM development in the Dacun Block needs a large depressurization of reservoir pressure due to the low ratio (avg. 0.37) of critical desorption pressure to reservoir pressure.

Objective Previous studies have shown a relationship between retinopathy and cognition including population with and without chronic kidney disease (CKD) but data regarding peritoneal dialysis (PD) are limited. This study aims to investigate the relationship between retinopathy and cognitive impairment in patients undergoing peritoneal dialysis (PD).Methods In this observational study, we recruited a total of 107 participants undergoing PD, consisting of 48 men and 59 women, ages ranging from 21 to 78 years. The study followed a cross-sectional design. Retinal microvascular characteristics, such as geometric changes in retinal vascular including tortuosity, fractal dimension (FD), and calibers, were assessed. Retinopathy (such as retinal hemorrhage or microaneurysms) was evaluated using digitized photographs. The Modified Mini-Mental State Examination (3MS) was performed to assess global cognitive function.Results The prevalence rates of retinal hemorrhage, microaneurysms, and retinopathy were 25%, 30%, and 43%, respectively. The mean arteriolar and venular calibers were 63.2 and 78.5 µm, respectively, and the corresponding mean tortuosity was 37.7 ± 3.6 and 37.2 ± 3.0 mm−1. The mean FD was 1.49. After adjusting for age, sex, education, mean arterial pressure, and Charlson index, a negative association was revealed between retinopathy and 3MS scores (regression coefficient: −3.71, 95% confidence interval: −7.09 to −0.33, p = 0.03).Conclusions Retinopathy, a condition common in patients undergoing PD, was associated with global cognitive impairment. These findings highlight retinopathy, can serve as a valuable primary screening tool for assessing the risk of cognitive decline.

Acute kidney injury (AKI) is a syndrome characterized by rapid loss of renal excretory function. Its underlying mechanisms remain unclear. Pyroptosis, a form of programmed cell death, plays an important role in AKI. It is characterized by cell swelling and membrane rupture, triggering the release of cellular contents and activating robust inflammatory responses. Carnosine, a dipeptide with antioxidant and anti-inflammatory properties, has therapeutic effects in AKI. However, the mechanism by which carnosine treats AKI-associated pyroptosis remains unexplored. In this study, we investigated the protective effect of carnosine on renal tubule cells using in vivo and in vitro models of AKI. We found that carnosine therapy significantly alleviated altered serum biochemical markers and histopathological changes in mice with cisplatin-induced AKI. It also reduced the levels of inflammation and pyroptosis. These results were consistent with those seen in human kidney tubular epithelial cells (HK-2) treated with cisplatin. Through molecular docking and cellular thermal shift assay, we identified caspase-1 as a target of carnosine. By knocking down caspase-1 in HK-2 cells using caspase-1 siRNA, we demonstrated that carnosine did not exhibit a protective role in cisplatin-induced HK-2 cells. This study provides the first evidence that carnosine alleviates damage to kidney tubular epithelial cells by targeting caspase-1 and inhibiting pyroptosis. Therefore, carnosine holds promise as a potential therapeutic agent for AKI, with caspase-1 representing an effective therapeutic target in this pathology.

In order to study the effect of typical pioneer herb plants in the metal smelting slag dump on the nutrients and heavy metal forms of the slag, the pioneer herb (Trifolium repens, Lolium perenne) rhizosphere microdomains on the lead-zinc smelting slag dump that has carried out vegetation reconstruction for 5 years were used as the research object, analyzing the differentiation characteristics of heavy metal content, occurrence forms and nutrients in two kinds of herbaceous plant rhizosphere micro-domain waste residues with different particle sizes (5 mm) during the ecological restoration process. The results showed that the plant nutrients in the waste residue were mainly distributed in the small particle size waste residue ryegrass> control, and showed obvious rhizosphere effects (rhizosphere> non rhizosphere). Two phytoremediation effects significantly affect the heavy metal content of waste residues and the distribution of their occurrence forms in different particle sizes: (1) The content of Pb and Cu in clover rhizosphere waste residue was significantly lower than that of the control, and promoted the conversion of Cd to residue; (2) The content of Cu and Cd in ryegrass rhizosphere waste residues with different particle sizes is redistributed, and the content in the fine particle size (

This study aimed to investigate the activating mechanism of the NLRP3 inflammasome in trichloroethylene-sensitized mice. In total, 88 BALB/c female mice were used to establish the trichloroethylene (TCE)-sensitized mouse model. Some of the mice received MitoTEMPO, MCC 950 or soluble recombinant CD59-Cys to inhibit mitochondrial reactive oxygen species (mtROS) production, NLRP3 assembly, or C5b-9 formation. Mouse tubular epithelial cell expression levels of NLRP3, ASC, Caspase 1, IL-1β, IL-18 and mitochondrial antiviral signaling protein (MAVS) were detected by western blot. Mitochondrial numbers, membrane potential (ΔΨm) and mtROS were detected by using MitoScene Green II, JC-1 dye and MitoSOX Red indicator, respectively. Tubular epithelial cell calcium levels were detected by a Fluo-8 no wash calcium assay kit. Human kidney-2 (HK-2) cells were cultured and stimulated by C5b6 and normal human serum (NHS) to verify the role of C5b-9-induced mitochondrial ROS in activating NLRP3 inflammasome. Urine α1-MG, β2-MG, and mtROS production and calcium levels were increased, while mitochondrial numbers were decreased in TCE-sensitized positive mice. After treatment with MitoTEMPO, renal tubular injury was alleviated, JC-1 fluorescence and mitochondrial numbers were significantly increased, and mitochondrial ROS were inhibited. The NLRP3 inflammasome was activated in TCE-sensitized positive mice, while Mito TEMPO inhibited MAVS expression and NLRP3 inflammasome activation. The in vitro studies proved that C5b-9 can induce mtROS release and activate the assembly of NLRP3 inflammasome in HK-2 cells. In conclusion, in TCE-sensitized positive mouse renal tubular epithelial cells, C5b-9 caused calcium influx and thus induced mitochondrial injury and mtROS overexpression, finally inducing MAVS expression and NLRP3 inflammasome activation and kidney injury.

Background Glomerular IgG deposition in patients with IgA nephropathy (IgAN) has been shown to be associated with poor renal survival; however, most published studies to date are too small-scale and inconsistent to provide guidance for clinical practice. Methods Based on renal biopsy findings, 742 patients were divided into the following groups: (i) IgA deposition alone (IgA) vs IgA + IgG deposition (IgA + IgG) and (ii) IgG co-deposition confined to the mesangium vs mesangium + capillary loops (CLs). The clinicopathological variables at biopsy and renal outcome were assessed. Results Of the 742 patients, 182 had IgG co-deposition and 51 had IgG deposits in the mesangium + CLs. Patients with IgG co-deposition were associated with severe clinical and pathological lesions, especially those with a location of IgG deposits in the mesangium +CLs. Kaplan–Meier analysis revealed that a lower renal cumulative survival rate was present in both patients with IgG co-deposition and those with a location of IgG deposits in the mesangium + CLs (all p

Acid mine drainage (AMD) causes environmental pollution that affects many countries with historic or current mining industries. The eco-remediation system (RW) which combined surface floating wetlands and bottom anaerobic sediments (SFW-BAS) was selected for AMD-contaminated lakes (AMDW). Meanwhile, AMDW and nature aquatic ecosystems (NW) were set as the control groups, respectively. The parameters, including pH, Eh, Fe, Mn, SO42−, and the degradation rate of the native dominant plant litter were investigated to assess the effects of remediation. The results showed that the average of pH, Eh, and EC, was 2.73, 484.08 mv, and 2395.33 μs·cm−1, respectively. The average content of SO42−, Fe, Mn, Cu, Zn, and Pb was 2190 mg·L−1, 40.2 mg·L−1, 4.6 mg·L−1, 249.2 μg·L−1, 1563 μg·L−1, and 112.9 μg·L−1, respectively. The degradation rate of plant litters in AMDW ranged from 14.5% to 22.6%. However, RW ultimately improved the water quality and the degradation of litters. RW has a good effect on buffering the acidity, ranging from 3.96 to 7.41. The pH of RW (6.14) is close to that of NW (7.41). The average content of SO42−, Fe, Mn, Cu, Zn, and Pb was 2071 mg·L−1, 3.4 mg·L−1, 2.4 mg·L−1, 85.3 μg·L−1, 607.4 μg·L−1, and 47.8 μg·L−1, respectively, which showed good pollutant removal performance. The degradation rate of plant litters in RW ranged from 27.8% to 32.6%. Therefore, RW can be used to remediate AMDW.

Purpose Encapsulating Peritoneal Sclerosis (EPS) is the most serious complication of long-term peritoneal dialysis (PD), which considerably reduces the patient’s quality of life, leading to patients discontinuing PD. Considering these negative effects, it is necessary to systematically review and determine the risk factors of EPS. Methods The PubMed, Embase, Web of Science, Cochrane Library, and China Biology Medicine (CBM) were searched from their inception to January 1st, 2022, and the bibliographies from the citations of relevant articles were manually searched. The ROBINS-I (Risk of Bias in Non-randomized studies of Interventions) tool was used to evaluate the risk of bias of included studies. Results Ten studies involving 12595 participants were included in this meta-analysis. The results revealed that a younger age at PD onset (MD = -7.70, 95% CI, -11.53~-3.86), a higher transporter (MD = 0.13, 95% CI, 0.09~0.18), a longer PD duration (SMD = 1.15, 95% CI, 0.68~1.61), a longer peritonitis duration (MD = 12.66, 95% CI, 3.85~21.47), and history of glomerulonephritis (OR = 1.42, 95% CI, 1.02~1.97) were significant risk factors for EPS. However, sex, use of icodextrin, the number of peritonitis episodes, and history of multicystic kidney disease did not affect the risk of EPS. Conclusions This review provides a scientific basis for further understanding the etiology of PD-related EPS and improving prevention strategies. More high-quality studies are necessary to validate this paper’s findings.

Lanmuchang mercury-thallium mine, a typical polymetallic mine is located in southwestern Guizhou, China, is the most serious and typical area resulted from multi-metal contamination (Tl, Hg, As, and Sb). After the mercury-thallium mining, a large area of surrounding rocks such as argillaceous sandstone with high contents of Tl, Hg, As, and Sb is exposed to air. Weathering caused the argillaceous sandstone to form different weathering layers, including the grey-black external layer, the brown-yellow middle layer and the gray-white inner layer, and the external layer was enriched with higher heavy metals. However, the reason of heavy metal migration and transformation in argillaceous sandstone caused by weathering is unclear. The objective of this paper was to investigate the migration, transformation and release characteristics of Tl, Hg, As, and Sb in argillaceous sandstone during the weathering. The results indicated that weathering not only promoted an acidic oxidation environment in argillaceous sandstone, but also increased its specific surface area, pore volume and hydrophilicity, which are beneficial to the permeability of oxygen and etching liquids during the process of weathering and leaching. Meanwhile, weathering led to the transformation or decomposition of hydrophilic groups, such as -OH and -C˭O in the grey-black external layer of argillaceous sandstone, resulting in the further release of heavy metals bound to these groups. The concentration of Tl, Hg, As, and Sb in the leaching solution of argillaceous sandstone represented a positive correlation with that of Fe, Ca, Mg at different levels, indicating that Tl, Hg, As, and Sb were released with the dissolution of Fe, Ca and Mg during weathering and leaching. In summary, these results indicated that weathering caused the dissolution and migration of heavy metals in the argillaceous sandstone. Tl, Hg, As, and Sb migrated from the grey-white inner layer to the grey-black external layer and partially adsorbed by free alumina (Ald), jarosite and Ca-bearing minerals, showing enrichment phenomena, partially released into the environment, causing environmental pollution.

We have previously reported that the CNDP1 (CTG)5 allele affords protection against diabetic nephropathy (DN) in patients with Type 2 diabetes (T2DM) of Caucasian origin. Because the incidence of ESRD attributable to both Type 1 diabetes (T1DM) and T2DM is higher among South Asian than Caucasian people, the present study assessed relevant CNDP1 polymorphisms and their association with metabolic parameters in the Chinese Han population. To this end, the (CTG)n allele distribution along with 5 relevant SNPs in the CNDP1 gene, previously reported to be associated with DN in non (CTG)5 carriers of Afro-American ethnicity, were determined in 663 healthy individuals. The (CTG)6 homozygous genotype was the most prevalent (84.5%) genotype in the Chinese Han population. The (CTG)5 and (CTG)4 alleles were present in a small minority of individuals accounting for 15.2% and 0.3% of genotypes with at least one (CTG)5 or one (CTG)4 allele, respectively. Only 0.5% of individuals carried the homozygous (CTG)5 genotype and individuals carrying the homozygous (CTG)4 genotype were not found. The minor allele frequencies (MAFs) of the 5 SNP were 0.197 (C allele for rs4892247), 0.0855 (C allele for rs62099905), 0.085 (G allele for rs62099906), 0.066 (T allele for rs62099907), and 0.18 (A allele for rs72979715). All the SNPs except rs4892247 genotypes were in the Hardy-Weinberg equilibrium. Neither the (CTG)n polymorphism nor the latter three SNPs reached significance when compared with different metabolic parameters. In contrast, individuals with the TT genotype of rs62099905 presented lower fasting blood glucose but higher HbA1c levels. In conclusion, the rs62099905 in the CNDP1 gene is associated with serum glucose levels in the healthy Chinese Han population, while for the CNDP1 (CTG)n polymorphism, no association with serological parameters was found.

Background/Aims: Risk factor studies for acute kidney injury (AKI) in China are lacking, especially those regarding non-traditional risk factors, such as laboratory indicators. Methods: All adult patients admitted to 38 tertiary and 22 secondary hospitals in China in any one month between July and December 2014 were surveyed. AKI patients were screened according to the Kidney Disease: Improving Global Outcomes’ definition of AKI. Logistic regression was used to analyze the risk factors for AKI, and Cox regression was used to analyze the risk of in-hospital mortality for AKI patients; additionally, a propensity score analysis was used to reconfirm the risk factors among laboratory indicators for mortality. Results: The morbidity of AKI was 0.97%. Independent risk factors for AKI were advancing age, male gender, hypertension, and chronic kidney disease. All-cause mortality was 16.5%. The predictors of mortality in AKI patients were advancing age, tumor, higher uric acid level and increases in Acute Physiologic Assessment and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores. The hazard ratio (HR) for mortality with uric acid levels > 9.1 mg/dl compared with ≤ 5.2 mg/dl was 1.78 (95% CI: 1.23 to 2.58) for the AKI patients as a group, and was 1.73 (95% CI: 1.24 to 2.42) for a propensity score-matched set. Conclusion: In addition to traditional risk factors, uric acid level is an independent predictor of all-cause mortality after AKI.

Total glucosides of paeony (TGP), extracted from the root of Paeonia lactiflora pall, has been shown to have ant-inflammatory and antioxidative actions. The aims of this study were to elucidate the renoprotective effect of TGP and its mechanism in experimental diabetes. Streptozotocin-induced diabetic rats were treated with TGP for 8 weeks. Treatment with TGP at 50, 100, and 200 mg/kg significantly lowered 24-h urinary albumin excretion rate in diabetic rats. TGP treatment in all doses markedly attenuated glomerular volume, and treatment with TGP at 100 and 200 mg/kg markedly reduced indices for tubulointerstitial injury in diabetic rats. Western blot analysis showed that the expressions of 1α (IV) collagen, intercellular adhesion molecule (ICAM)-1, interleukin (IL)-1, tumor necrosis factor (TNF)-α, NF-κB p65, and 3-nitrotyrosine (3-NT) protein were increased in the kidneys of diabetic rats; the increases in these proteins were all dose-dependently and significantly inhibited by TGP treatment. The expression of nephrin protein was significantly reduced in the kidneys from diabetic rats and markedly increased by TGP treatment. The expression of transforming growth factor (TGF)-β1 protein in the kidney was also significantly increased in diabetic rats, which was significantly inhibited by treatment with TGP at all doses. Our data suggest that TGP treatment ameliorates early renal injury via the inhibition of expression of ICAM-1, IL-1, TNF-α, and 3-NT in the kidneys of diabetic rats. Keywords:: diabetic nephropathy, total glucosides of paeony (TGP), intercellular adhesion molecule (ICAM)-1, interleukin (IL)-1, tumor necrosis factor (TNF)-α