External Validation of the International IgA Nephropathy Prediction Tool in Older Adult Patients.

Purpose: The International IgA Nephropathy Prediction Tool (IIgAN-PT) can predict the risk of End-stage renal disease (ESRD) or estimated glomerular filtration rate (eGFR) decline ≥ 50% for adult IgAN patients. Considering the differential progression between older adult and adult patients, this study aims to externally validate its performance in the older adult cohort. Patients and Methods: We analyzed 165 IgAN patients aged 60 and above from six medical centers, categorizing them by their predicted risk. The primary outcome was a ≥50% reduction in estimated glomerular filtration rate (eGFR) or kidney failure. Evaluation of both models involved concordance statistics (C-statistics), time-dependent receiver operating characteristic (ROC) curves, Kaplan-Meier survival curves, and calibration plots. Comparative reclassification was conducted using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results: The study included 165 Chinese patients (median age 64, 60% male), with a median follow-up of 5.1 years. Of these, 21% reached the primary outcome. Both models with or without race demonstrated good discrimination (C-statistics 0.788 and 0.790, respectively). Survival curves for risk groups were well-separated. The full model without race more accurately predicted 5-year risks, whereas the full model with race tended to overestimate risks after 3 years. No significant reclassification improvement was noted in the full model without race (NRI 0.09, 95% CI: -0.27 to 0.34; IDI 0.003, 95% CI: -0.009 to 0.019). Conclusion: : Both models exhibited excellent discrimination among older adult IgAN patients. The full model without race demonstrated superior calibration in predicting the 5-year risk.

Association of VEGF+936 C/T Polymorphism with Susceptibility to Type 2 Diabetic Retinopathy: A Meta-Analysis.

The objective of this study is to explore the relationship between the vascular endothelial growth factor (VEGF)+936 C/T polymorphism and the risk of type 2 diabetic retinopathy (T2DR) by a method of meta-analysis. Six online databases were queried to identify studies investigating the VEGF+936 C/T polymorphism that influenced T2DR up to August 2023. The statistical tool of the pooled data was adopted using Stata 15.0 software. The experimental group comprised patients with T2DR, while patients with type 2 diabetes mellitus without retinopathy were considered as the controls. The odds ratio (OR) was utilized as effect size. Eight eligible publications were identified in this review, including 1546 patients with T2DR. The combined results revealed that the VEGF+936 C/T polymorphism was significantly associated with the T2DR risk under the allelic (C/T: OR=0.54, p<0.001), the dominant (CC+CT/TT: OR=0.37, p<0.001), recessive (CC/CT+TT: OR=0.52, p=0.001), homozygous (CC/TT: OR=0.31, p<0.001), and heterozygous (CT/TT: OR=0.55, p=0.005) gene models. No significant correlation was observed regarding the VEGF+936 C/T polymorphism that contributed to the risk of proliferative diabetic retinopathy (PDR) versus non-PDR. In conclusion, the VEGF+936 C/T polymorphism significantly contributed to the T2DR risk. Specifically, at the VEGF+936 C/T locus, the presence of allele C and genotypes CC, CT, and CC+CT were found to be associated with a reduced risk of T2DR.

Piceatannol Protects against High Glucose-Induced Injury of Renal Tubular Epithelial Cells via Regulating Carbonic Anhydrase 2.

INTRODUCTION: We here evaluated the efficacy of piceatannol (PIC) in high glucose (HG)-induced injury of renal tubular epithelial cells HK-2. METHODS: After the establishment of an HG-induced cell injury model and the treatment with PIC at both high and low concentrations and/or acetazolamide (ACZ, the inhibitor of carbonic anhydrase 2 [CA2]), MTT and flow cytometry assays were carried out to confirm the viability and apoptosis of HK-2 cells. The levels of oxidative stress markers lactate dehydrogenase (LDH), malondialdehyde (MDA), and reactive oxygen species (ROS), the ratio of glutathione/oxidized glutathione (GSH/GSSG), and the CA2 activity were determined. Both quantitative reverse-transcription polymerase chain reaction and Western blot were used to calculate the expressions of CA2 (the predicted target gene of PIC via intersecting the data from bioinformatic analyses) and AKT pathway-related (phosphatase and tensin homolog [PTEN], phosphorylated [p]-AKT, AKT) and apoptosis-related proteins (Bcl-2 and cleaved caspase-3). RESULTS: HG suppressed cell viability and the levels of GSH/GSSG ratio, CA2, pThr308-AKT/AKT, pSer473-AKT/AKT, and Bcl-2, while promoting cell apoptosis, the levels of LDH, MDA, and ROS, and the expressions of PTEN and cleaved caspase-3. All effects of HG were reversed by PIC at a high concentration. CA2 was predicted and identified as the target of PIC. In HG-treated HK-2 cells, additionally, ACZ reversed the effects of PIC on the viability, apoptosis, and levels of both oxidative stress markers and AKT pathway- and apoptosis-related factors. CONCLUSION: PIC protects against HG-induced injury of HK-2 cells via regulating CA2.

The Association of Methylenetetrahydrofolate Reductase (MTHFR) A1298C Gene Polymorphism with Susceptibility to Diabetic Nephropathy: A Meta-Analysis.

This meta-analysis was conducted to investigate the association between MTHFR A1298C polymorphism and susceptibility to diabetic nephropathy. PubMed, Embase, Web of Science, Cochrane Library, China national knowledge infrastructure (CNKI) and China Wanfang database were searched for studies on the association between MTHFR A1298C single nucleotide polymorphism and susceptibility to diabetic nephropathy until May 2022. Data were analyzed by Stata 15.0 software. Odds ratio (OR) was used as the effect size. A total of 7 articles were identified, including 1287 cases in the diabetic nephropathy group and 1431 cases in the control group. The pooled OR of allele C at MTHFR A1298C was 1.28 (95% CI: 1.02-1.59, p=0.03) compared with allele A. The pooled OR values of dominant, and heterozygous genetic models were 1.45 (95% CI: 1.13-1.86), and 1.42 (95% CI: 1.19-1.70), respectively, and the differences were all statistically significant. There was no statistical significance in the recessive (OR=1.06, 95% CI: 0.62-1.82), and homozygous gene inheritance models (OR=1.29, 95% CI: 0.72-2.31). In conclusion, MTHFR A1298C polymorphism is associated with susceptibility to diabetic nephropathy. Allele C, genotype CC+AC, and AC at MTHFR A1298C locus can increase the risk of diabetic nephropathy.

Efficacy and safety of artesunate for patients with IgA nephropathy: a study protocol for a multicenter, double-blind, randomized, placebo-controlled trial.

BACKGROUND: IgA nephropathy is the most common glomerular disease and is a common cause of progression to end-stage renal disease in patients with kidney diseases. Proteinuria levels are critical for the prognosis of patients with IgA nephropathy, but many patients are still unable to effectively control their proteinuria levels after receiving RAAS blockers. Antimalarial drugs have shown good efficacy in the treatment of kidney disease in previous studies; however, there have been no strictly designed randomized controlled trials to confirm the clinical efficacy of artesunate for treating IgA nephropathy patients. Therefore, we designed this clinical trial to compare the effect of artesunate versus placebo in patients with IgA nephropathy. METHODS: This study is a randomized, double-blind, three-group-parallel, placebo-controlled clinical trial. One hundred and twenty eligible IgA nephropathy patients at risk of progression will be randomly divided into the artesunate 100-mg group, artesunate 50-mg group, and placebo group. Changes in proteinuria and renal function will be measured 6 months after the intervention. The levels of Gd-IgA1 and anti-Gd-IgA1 in the patient's blood will also be tested to explore the possible immune mechanisms. DISCUSSION: Clinical evidence supporting artesunate treatment of IgA nephropathy is currently lacking, and we expect that the results of this trial will provide high-quality clinical evidence for artesunate as a treatment option for IgA nephropathy in the future. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000038104 . Registered on 10 September 2020.

Attributable risk of all-cause mortality in hypertensive adults based on disease risk prediction model: A Chinese cohort study.

BACKGROUND: The aim of this study was to estimate the attributable risk for all-cause mortality in hypertensive adults living in Beijing, China. METHODS: We conducted a prospective cohort study on the basis of the disease risk prediction model, which included 3006 hypertensive patients aged 50 and over who participated in the annual health examination from thirty-eight community health centers were randomly selected from all 53 community health centers in Dongcheng district of Beijing in China. This cohort study was conducted from January 1, 2013 to June 31, 2018 in these community health centers. Data included age, gender, education level, BMI, smoking and drinking status, renal function, diabetes mellitus (DM), coronary heart disease, levels of blood pressure, use of medications, and blood lipid levels. RESULTS: the follow-up time was 4.90±0.51 years. There were significant survival differences by gender, renal function (eGFR>90 vs. 60-90 vs. <60mL/min per 1.73m2), smoking (smoking vs. No smoking), hypertension severity (SBP≥140 or DBP≥r vs. SBP/DBP<140/90mmHg), education level (<6 vs. 6-12 vs. >12 years), coronary heart disease (CHD) (CHD vs. NO CHD). In the multivariate Cox proportional hazard analysis, the prognostic factors of all-cause mortality in hypertensive patients were male [HR 1.662, 95% CI 1.110-2.489, p=0.014], educational level<6 years [HR 2.044, 95% CI 1.164-3.591, p 0.013], age ≥65 years [HR 3.092, 95% CI 1.717-5.571, p<0.001], smoking [HR 1.885, 95% CI 1.170-3.309, p=0.009], eGFR<60mL/min per 1.73m2 [HR 3.591, 95% CI 2.023-6.371, p<0.001]. CONCLUSIONS: we conclude that decreasing eGFR, increasing age, smoking, low education and gender (male) are significant and independent risk factor for mortality in hypertension for this urban cohort. Recommendations may include protecting renal function, providing patient education, and cessation of smoking. It highlights that early preventive measures are needed to detect kidney impairment and protect renal function. It also suggests that earlier smoking cessation may be important for hypertensive patients.

Activation of disease resistance against Botryosphaeria dothidea by downregulating the expression of MdSYP121 in apple.

In plants, the vesicle fusion process plays a vital role in pathogen defence. However, the importance of the vesicle fusion process in apple ring rot has not been studied. Here, we isolated and characterised the apple syntaxin gene MdSYP121. Silencing the MdSYP121 gene in transgenic apple calli increased tolerance to Botryosphaeria dothidea infection; this increased tolerance was correlated with salicylic acid (SA) synthesis-related and signalling-related gene transcription. In contrast, overexpressing MdSYP121 in apple calli resulted in the opposite phenotypes. In addition, the results of RNA sequencing (RNA-Seq) and quantitative real-time PCR (qRT-PCR) assays suggested that MdSYP121 plays an important role in responses to oxidation-reduction reactions. Silencing MdSYP121 in apple calli enhanced the expression levels of reactive oxygen species (ROS)-related genes and the activity of ROS-related enzymes. The enhanced defence response status in MdSYP121-RNAi lines suggests that syntaxins are involved in the defence response to B. dothidea. More importantly, we showed that MdSYP121 forms a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex with MdSNAP33, and the complex may participate in regulating resistance to B. dothidea. In conclusion, by regulating the interaction of SA pathway and oxidation-reduction process, MdSYP121 can influence the pathogen infection process in apple.

Hemothorax caused by replacement of hemodialysis catheter: A case report.

Central venous catheters (CVC) are widely used in clinics to gain vascular access, but the risk and prevalence of catheter-related complications remains a serious issue. We report a long-term dialysis catheter accidentally inserted into the mediastinum via the right jugular vein in a hemodialysis patient. We also review complications associated with vascular catheterization and propose immediate therapeutic interventions for such cases.

Decellularized ovine arteries as biomatrix scaffold support endothelial of mesenchymal stem cells.

The differentiation rate of adipose-derived mesenchymal stem cells (Ad-MSCs) into endothelial cells is always lower under normal condition, which limits further clinical application of Ad-MSCs for angiogenesis regenerative medicine and needs to be enhanced. In the present study, the tissue-specific-derived decellularized ovine arteries matrix (DCS) was used as scaffold to investigate the pro-endothelial differentiation ability of decellularized ovine arteries matrix as well as the underlying mechanisms. The prepared decellularized ovine arteries matrix by the combination of enzymatic and chemical decellularization approaches preserved macroscopic 3D architecture, native composition and ultrastructure of natural ovine arteries. The RT-PCR, histopathological and immunofluorescence assay results suggested that DCS could increase the proliferation ability of MSC. What's more, the DCS could also induce the endothelial differentiation of MSC, which was further enhanced by adding VEGF. Our results showed that natural 3D matrix from decellularized ovine arteries could induce the endothelial differentiation of AD-MSCs alone or with the combination of VEGF. Our results indicated that the decellularized ovine arteries matrix would serve as an efficient culture system for promoting endothelial differentiation of Ad-MSCs.

Hypoxia-pretreated human MSCs attenuate acute kidney injury through enhanced angiogenic and antioxidative capacities.

Hypoxia preconditioning has been confirmed as an effective strategy to enhance the therapeutic potentials of mesenchymal stem cells (MSCs), such as for myocardial ischemia. However, whether hypoxia preconditioning would produce beneficial effects on MSC-based renal repair has not been demonstrated. In the study, we aimed to determine the feasibility and efficacy of hypoxia preconditioning to enhance MSC-based therapy of acute kidney injury (AKI). MSCs were isolated from human adipose tissues. The paracrine effects of MSCs under normoxia and hypoxia were determined in vitro. Rats of AKI were induced by kidney I/R surgery and randomly divided into three groups: I/R control receiving PBS injection; MSC group receiving normal MSC injection; hypoMSC group receiving hypoxia-preconditioned MSC injection. It was demonstrated in vitro that paracrine effects of MSCs were significantly enhanced, especially angiogenic factors. Dihydroethidium (DHE) staining showed that antioxidative activities of MSCs were significantly enhanced by hypoxia stimulation. Vascularization, apoptosis, and histological injury were all significantly improved in hypoMSC injected group compared with that in control and MSC injected groups. Finally, the renal function was also significantly improved in hypoMSC injected group compared with that in the other two groups as assessed by the serum creatinine and BUN levels.

A multicenter application and evaluation of the oxford classification of IgA nephropathy in adult chinese patients.

BACKGROUND: The Oxford classification of immunoglobulin A (IgA) nephropathy (IgAN) provides a histopathologic grading system that is associated with kidney disease outcomes independent of clinical features. We evaluated the Oxford IgAN classification in a large cohort of patients from China. STUDY DESIGN: Retrospective study. SETTING & PARTICIPANTS: 1,026 adults with IgAN from 18 referral centers in China. Inclusion criteria and statistical analysis were similar to the Oxford study. PREDICTORS: Histologic findings of mesangial hypercellularity score, endocapillary proliferation, segmental sclerosis or adhesion, crescents, necrosis, and tubular atrophy/interstitial fibrosis. Clinical features, blood pressure, estimated glomerular filtration rate (eGFR), proteinuria, and treatment modalities. OUTCOMES: Time to a 50% reduction in eGFR or end-stage renal disease (the combined event); the rate of eGFR decline (slope of eGFR); proteinuria during follow-up. RESULTS: Compared with the Oxford cohort, the Chinese cohort had a lower proportion of patients with mesangial hypercellularity (43%) and endocapillary proliferation (11%), higher proportion with segmental sclerosis or adhesion (83%) and necrosis (15%), and similar proportion with crescents (48%) and tubular atrophy/interstitial fibrosis (moderate, 24%; severe, 3.3%). During a median follow-up of 53 (25th-75th percentile, 36-67) months, 159 (15.5%) patients reached the combined event. Our study showed that patients with a mesangial hypercellularity score higher than 0.5 were associated with a 2.0-fold (95% CI, 1.5-2.8; P<0.001) higher risk of the combined event than patients with a score of 0.5 or lower. Patients with tubular atrophy/interstitial fibrosis of 25%-50% and >50% versus <25% were associated with a 3.7-fold (95% CI, 2.6-5.1; P<0.001) and 15.1-fold (95% CI, 9.5-24.2; P<0.001) higher risk of the combined event, respectively. Endocapillary proliferation, glomerular crescents, and necrosis were not significant. LIMITATIONS: Retrospective study; the therapeutic interventions were miscellaneous. CONCLUSIONS: We confirmed the associations of mesangial hypercellularity and tubular atrophy/interstitial fibrosis with kidney disease outcomes.