Urinary complement profile in IgA nephropathy and its correlation with the clinical and pathological characteristics

Background and objectivesThe activated complement profile in IgA nephropathy (IgAN) is still unclear. Our study investigated the profile of urinary complements in IgAN patients and its correlations with clinical and pathological characteristics.MethodsUrinary protein abundance was detected by liquid chromatography-tandem mass spectrometry (LC–MS/MS) in 50 IgAN, 50 membranous nephropathy (MN), and 68 healthy controls (HC). Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify differentially expressed proteins in IgAN patients. The differentially expressed complement proteins were screened in IgAN patients, and their correlations with laboratory or pathological parameters were analyzed. Thereafter, 7 complement components were validated by enzyme-linked immunosorbent assay (ELISA) in the urine samples of 45 IgAN patients.ResultsThere were 786 differentially expressed proteins between IgAN and HC. KEGG analysis showed that differentially expressed urinary proteins in IgAN were enriched with complement. Of these, 67% of urinary complement protein abundance was associated with the estimated glomerular filtration rate. The urinary complement-related protein collectin12 (colec12), complement H factor (CFH), complement H factor-related protein 2 (CFHR2), and complement B factor (CFB) were positively correlated with serum creatinine; colec12, CFHR2, CFB, and C8g were positively correlated with glomerulosclerosis; CFH, CFHR2, C8g, and C9 were positively correlated with tubular atrophy/interstitial fibrosis.ConclusionAbnormally increased components of complement pathways significantly correlate with reduced renal function, proteinuria, and renal histological damage in IgAN. It could provide a potential biomarker panel for monitoring IgAN and provide clues for therapeutic choice targeting complement system of IgAN patients

The genetic variants at the HLA-DRB1 gene are associated with primary IgA nephropathy in Han Chinese

BACKGROUND: Immunoglobulin A nephropathy (IgAN), an immune-complex-mediated glomerulonephritis defined immunohistologically by the presence of glomerular IgA deposits, is the most common primary glomerular disease worldwide and a significant cause of end-stage renal disease. Familial clustering of patients with IgAN suggests a genetic predisposition. METHODS: In this study, 192 patients with IgAN and 192 normal controls in the Sichuan cohort and 935 patients with IgAN and 2,103 normal controls in the Beijing cohort were investigated. HLA-DRB1*01–DRB1*10 specificities were genotyped by the PCR–SSP technique in both cohorts. Based on the HLA-DRB1*04-positive results, the subtypes of HLA-DRB1*04 were analyzed using sequencing-based typing (SBT) in 291 IgAN cases and 420 matched controls. RESULTS: The frequency of HLA-DRB1*04 in the IgAN group was significantly higher than that in the control group (0.129 vs. 0.092, P = 8.29 × 10(-5), odds ratio (OR) =1.381, 95% confidence interval (CI) 1.178–1.619). Other alleles at the HLA-DRB1 locus were observed with no significant differences between the case and control groups. The dominant alleles of the HLA-DRB1*04 subtypes were DRB1*0405 in both cohorts. The frequencies of HLA-DRB1*0405 and 0403 were significantly increased in the patients compared to healthy subjects. CONCLUSION: HLA-DRB1*04 was significantly associated with primary IgAN in Chinese population. This result implies that HLA-DRB1 gene plays a major role in primary IgAN

ImageCAS: A Large-Scale Dataset and Benchmark for Coronary Artery Segmentation based on Computed Tomography Angiography Images

Cardiovascular disease (CVD) accounts for about half of non-communicable diseases. Vessel stenosis in the coronary artery is considered to be the major risk of CVD. Computed tomography angiography (CTA) is one of the widely used noninvasive imaging modalities in coronary artery diagnosis due to its superior image resolution. Clinically, segmentation of coronary arteries is essential for the diagnosis and quantification of coronary artery disease. Recently, a variety of works have been proposed to address this problem. However, on one hand, most works rely on in-house datasets, and only a few works published their datasets to the public which only contain tens of images. On the other hand, their source code have not been published, and most follow-up works have not made comparison with existing works, which makes it difficult to judge the effectiveness of the methods and hinders the further exploration of this challenging yet critical problem in the community. In this paper, we propose a large-scale dataset for coronary artery segmentation on CTA images. In addition, we have implemented a benchmark in which we have tried our best to implement several typical existing methods. Furthermore, we propose a strong baseline method which combines multi-scale patch fusion and two-stage processing to extract the details of vessels. Comprehensive experiments show that the proposed method achieves better performance than existing works on the proposed large-scale dataset. The benchmark and the dataset are published at https://github.com/XiaoweiXu/ImageCAS-A-Large-Scale-Dataset-and-Benchmark-for-Coronary-Artery-Segmentation-based-on-CT.Comment: 17 pages, 12 figures, 4 table

The analysis of APOL1 genetic variation and haplotype diversity provided by 1000 Genomes project

Abstract Background The APOL1 gene variants has been shown to be associated with an increased risk of multiple kinds of diseases, particularly in African Americans, but not in Caucasians and Asians. In this study, we explored the single nucleotide polymorphism (SNP) and haplotype diversity of APOL1 gene in different races provided by 1000 Genomes project. Methods Variants of APOL1 gene in 1000 Genome Project were obtained and SNPs located in the regulatory region or coding region were selected for genetic variation analysis. Total 2504 individuals from 26 populations were classified as four groups that included Africa, Europe, Asia and Admixed populations. Tag SNPs were selected to evaluate the haplotype diversities in the four populations by HaploStats software. Results APOL1 gene was surrounded by some of the most polymorphic genes in the human genome, variation of APOL1 gene was common, with up to 613 SNP (1000 Genome Project reported) and 99 of them (16.2%) with MAF ≥ 1%. There were 79 SNPs in the URR and 92 SNPs in 3’UTR. Total 12 SNPs in URR and 24 SNPs in 3’UTR were considered as common variants with MAF ≥ 1%. It is worth noting that URR-1 was presents lower frequencies in European populations, while other three haplotypes taken an opposite pattern; 3’UTR presents several high-frequency variation sites in a short segment, and the differences of its haplotypes among different population were significant (P < 0.01), UTR-1 and UTR-5 presented much higher frequency in African population, while UTR-2, UTR-3 and UTR-4 were much lower. APOL1 coding region showed that two SNP of G1 with higher frequency are actually pull down the haplotype H-1 frequency when considering all populations pooled together, and the diversity among the four populations be widen by the G1 two mutation (P 1 = 3.33E-4 vs P 2 = 3.61E-30). Conclusions The distributions of APOL1 gene variants and haplotypes were significantly different among the different populations, in either regulatory or coding regions. It could provide clues for the future genetic study of APOL1 related diseases

Effect of magnesium on vascular calcification in chronic kidney disease patients: a systematic review and meta-analysis

AbstractPurpose To evaluate the effects of magnesium (Mg) supplementation on vascular calcification (VC) in patients with chronic kidney disease (CKD).Methods PubMed, Embase, Cochrane Library, Medline, Web of Science, CNKI, VIP, and WanFang databases were searched from build to July 2022. Randomized controlled trials (RCT) and non-RCT related to whether Mg supplementation inhibits VC in patients with CKD were included. The literature was screened according to inclusion and exclusion criteria, and quality evaluation and data collection were performed. Meta-analysis was performed using Review Manager 5.4 software.Results 8 RCTs and 1 non-RCT studies with a total of 496 patients were eventually included. Compared to control groups, Mg supplementation increased serum Mg levels (SMD = 1.26, 95% CI: −0.70 to 1.82, p  0.05). Oral Mg reduced left (WMD=−0.06, 95% CI. −0.11 to −0.01, p = 0.03) and right (WMD=−0.07, 95% CI: −0.13 to −0.01, p = 0.02) carotid intima-media thickness (cIMT). Additionally, calcium (Ca) (SMD=−0.43, 95% CI: −0.74 to −0.11, p = 0.008) and parathyroid hormone (PTH) (SMD=−0.43, 95% CI: −0.75 to −0.11, p = 0.008) levels were reduced by increasing dialysate Mg concentration.Conclusions Mg supplementation increased serum Mg levels and reduced Ca, PTH, and cIMT, but it did not reduce VC scores in patients with CKD. This still requires further studies with larger samples to evaluate the effect of Mg supplementation on VC

Additional file 1: of The analysis of APOL1 genetic variation and haplotype diversity provided by 1000 Genomes project

Table S1. Size and function of APOL1 exons and introns. Table S2. The population and the number of samples in the different regions of people. Table S3. List of all SNP (MAF ≥ 1%) found in APOL1 gene region, their genomic positions on chromosome 22 and their allele frequencies presented in 1000 Genomes Project (Phase 3). Table S4. List of SNP (MAF ≥ 1%) found in APOL1 upstream regulatory region (URR), their genomic positions on chromosome 22 and their allele frequencies presented in 1000 Genomes Project (Phase 3). Table S5. List of SNP (MAF ≥ 1%) found in the APOL1 3′ untranslated region (3’UTR), their genomic positions on chromosome 22 and their allele frequencies presented in 1000 Genomes Project (Phase 3).Table S6. List of all SNP found in APOL1 coding region, their genomic positions on chromosome 22 and their allele frequencies presented in 1000 Genomes Project (Phase 3). Table S7. List of APOL1 coding haplotypes generated by Tag SNP (consider the two SNP of G1) which presenting a global frequency higher than 1%, considering all populations of the 1000 Genomes Project (Phase 3). Table S8. The most frequent APOL1 coding haplotypes and their frequencies (consider the two SNP of G1) among the 1000 Genomes Project (Phase 3) in different populations. Figure S1. Linkage disequilibrium plot generated by APOL1 gene SNPs (MAF ≥ 1%). Inter-SNP D’-values are displayed on the plot. Figure S2. 12 Tag SNP position in APOL1 gene. Figure S3. Spatial distribution of genetic variants at the APOL1 functional domain. (DOCX 531 kb

Association of high body mass index with development of interstitial fibrosis in patients with IgA nephropathy

Abstract Background The worldwide prevalence of obesity is increasing. Obesity is associated with a variety of chronic diseases, including chronic kidney disease. Several studies suggested that body mass index (BMI) could be an independent risk factor for progression of IgA nephropathy (IgAN). However, whether high BMI is associated with progression of IgAN remains uncertain. Methods This retrospective study included patients with biopsy proven IgAN from 2006 to 2017 in Sichuan Provincial People’s Hospital. BMI was categorized according to the WHO Asian guideline: underweight (< 18.5 kg/m2), normal weight (18.5-25 kg/m2), overweight (25-28 kg/m2) and obese (≥28 kg/m2). The main outcome was development of end-stage renal disease (ESRD) or a decline in eGFR by at least 30%. The association of BMI and IgAN progression was determined by propensity-score-matched cohort analysis. Results Four hundred eighty one patients with IgAN were finally enrolled in this study. The mean age was 37 ± 11 years and 40.3% were men. There was no significant difference in clinical and pathological characteristics among the four-group patients categorized by BMI. After matching with propensity scores, no significant correlation between BMI and renal outcomes was seen. However, compared with the reference group (18.5≦BMI≦25 kg/m2), being overweight (odd ratio [OR], 2.28; 95%CI: 1.06–4.88; P = 0.034) and obese (OR, 3.43; 95%CI: 1.06–11.04; P = 0.039) was associated with a high risk of interstitial fibrosis. In the cross figure demonstrating the association of BMI subgroup and interstitial fibrosis on renal outcomes, ORs of interstitial fibrosis groups were higher than those of no interstitial fibrosis. Compared with other BMI subgroups, patients with 18.5-25 kg/m2 had lowest ORs. Conclusions High BMI and interstitial fibrosis were associated with progression of IgAN. Interstitial fibrosis appears to be common in IgAN patients with elevated BMI

Microwave-assisted Kochetkov amination followed by permanent charge derivatization : A facile strategy for glycomics

We report a simple and rapid microwave-assisted method for the preparation of oligosaccharide-glycosylamines, followed by labelling with tris(2,4,6-trimethoxyphenyl)phosphonium acetic acid N-hydroxysuccinimide ester. The facile strategy introduced a permanent charge at the reducing end of the oligosaccharide. In combination of MALDI-MS, the detection limit for maltoheptaose was as low as 2 fmol \u3bcL\u207b\ub9.Peer reviewed: YesNRC publication: Ye