pH-mediated upregulation of AQP1 gene expression through the Spi-B transcription factor

Background: Bicarbonate-based peritoneal dialysis (PD) fluids enhance the migratory capacity and damage-repair ability of human peritoneal mesothelial cells by upregulating AQP1. However, little is known about the underlying molecular mechanisms. Results: Here we used HEK-293T cells to investigate the effect of pH on AQP1 gene transcription levels. We found that AQP1 mRNA levels increases with pH. Transfection of HEK-293T cells with luciferase reporter vectors containing different regions of the AQP1 promoter identified an upstream region in the AQP1 gene between − 2200 and – 2300 bp as an enhancer required for pH-mediated regulation of AQP1 expression. Site-directed mutagenesis of this specific promoter region revealed a critical region between − 2257 and − 2251 bp, and gene knock-down experiments and ChIP assays suggested that the Spi-B transcription factor SPIB is involved in pH-mediated regulation of AQP1 expression. Conclusions: We identified an upstream region in the AQP1 gene and the transcription factor SPIB that are critically involved in pH-mediated regulation of AQP1 expression. These findings provide the basis for further studies on the pH- and buffer-dependent effects of PD fluids on peritoneal membrane integrity and function

Analysis of the operational status of the three-level referral system for urologic ultrasound screening and risk factors for renal pelvic dilatation in high-risk children

BackgroundCongenital Anomalies of the Kidney and Urinary Tract (CAKUT) are the primary cause of end-stage renal disease in children, early diagnosis and treatment can significantly improve the kidney function. Among CAKUT, renal pelvis dilatation (RPD) due to various causes has the highest detection rate, which can be detected early by postnatal ultrasound screening. Since 2010, the Children's Hospital of Fudan University (CHFU), together with the Minhang District Maternal and Child Health Hospital (MCH) and Community Health Centres (CHCs) of Minhang District has created a three-level referral system for urological ultrasound screening. This study aims to describe the operation of a three-level referral system for ultrasound screening of CAKUT and to select risk factors of RPD in high-risk children.MethodsThe operation of the three-level referral system was assessed by analyzing the screening volume, screening rate, referral rate, and follow-up rate; risk factors of RPD in high-risk children were selected by chi-square test and multivariate logistic regression.ResultsA total of 16,468 high-risk children were screened in ten years, and the screening volume was maintained at about 1,500 cases per year; the screening rate showed a linear increase, from 36.8% in 2010 to 98.2% in 2019; the referral rate from the CHCs to the MCH was 89.9% significantly higher after 2015 than that of 84.7% from 2010 to 2015; the follow-up rate after 2015 was 71.0% significantly higher than that of 46.3% from 2010 to 2015. Multivariate logistic regression analysis showed that the risk of RPD was 1.966 times higher in males than in females, and the risk of moderate to severe RPD was 2.570 times higher in males than in females; the risk of RPD in preterm children was 1.228 times higher than that of full-term children; and the risk of RPD was 1.218 times higher in twins than in singles.ConclusionsThe screening volume of the three-level referral system has remained stable over a decade, with significantly higher screening, referral, and follow-up rates. Males, preterm, and twins are risk factors of RPD in high-risk children; males are also risk factors for moderate to severe RPD in high-risk children

Validation of the Oxford classification of IgA nephropathy for pediatric patients from China

BACKGROUND: The Oxford classification of IgA nephropathy (IgAN) provides a useful tool for prediction of renal prognosis. However, the application of this classification in children with IgAN needs validation in different patient populations. METHODS: A total of 218 children with IgAN from 7 renal centers in China were enrolled. The inclusion criteria was similar to the original Oxford study. RESULTS: There were 98 patients (45%) with mesangial proliferation (M1), 51 patients (23%) with endocapillary proliferation (E1), 136 patients (62%) with segmental sclerosis/adhesion lesion (S1), 13 patients (6%) with moderate tubulointerstitial fibrosis (T1 26-50% of cortex scarred), and only 2 patients (1%) with severe tubulointerstitial fibrosis (T2, >50% of cortex scarred). During a median follow-up duration of 56 months, 24 children (12.4%) developed ESRD or 50% decline in renal function. In univariate COX analysis, we found that tubular atrophy/interstitial fibrosis (HR 4.3, 95%CI 1.8-10.5, P < 0.001) and segmental glomerulosclerosis (HR 9.2 1.2-68.6, P = 0.03) were significant predictors of renal outcome. However, mesangial hypercellularity, endocapillary proliferation, crescents, and necrosis were not associated with renal prognosis. In the multivariate COX regression model, none of these pathologic lesions were shown to be independent risk factors of unfavorable renal outcome except for tubular atrophy/interstitial fibrosis (HR 2.9, 95%CI 1.0-7.9 P = 0.04). CONCLUSIONS: We confirmed tubular atrophy/interstitial fibrosis was the only feature independently associated with renal outcomes in Chinese children with IgAN

A new integrated and homogenized global monthly land surface air temperature dataset for the period since 1900

A new dataset of integrated and homogenized monthly surface air temperature over global land for the period since 1900 [China Meteorological Administration global Land Surface Air Temperature (CMA-LSAT)] is developed. In total, 14 sources have been collected and integrated into the newly developed dataset, including three global (CRUTEM4, GHCN, and BEST), three regional and eight national sources. Duplicate stations are identified, and those with the higher priority are chosen or spliced. Then, a consistency test and a climate outlier test are conducted to ensure that each station series is quality controlled. Next, two steps are adopted to assure the homogeneity of the station series: (1) homogenized station series in existing national datasets (by National Meteorological Services) are directly integrated into the dataset without any changes (50% of all stations), and (2) the inhomogeneities are detected and adjusted for in the remaining data series using a penalized maximal t test (50% of all stations). Based on the dataset, we re-assess the temperature changes in global and regional areas compared with GHCN-V3 and CRUTEM4, as well as the temperature changes during the three periods of 1900–2014, 1979–2014 and 1998–2014. The best estimates of warming trends and there 95% confidence ranges for 1900–2014 are approximately 0.102 ± 0.006 °C/decade for the whole year, and 0.104 ± 0.009, 0.112 ± 0.007, 0.090 ± 0.006, and 0.092 ± 0.007 °C/decade for the DJF (December, January, February), MAM, JJA, and SON seasons, respectively. MAM saw the most significant warming trend in both 1900–2014 and 1979–2014. For an even shorter and more recent period (1998–2014), MAM, JJA and SON show similar warming trends, while DJF shows opposite trends. The results show that the ability of CMA-LAST for describing the global temperature changes is similar with other existing products, while there are some differences when describing regional temperature changes

Study on Column-Top Seismic Isolation of Single-Layer Latticed Domes

In this paper, a single-layer lamella reticulated dome with reinforced concrete bearings was studied, and a method of column-top isolation was proposed to improve the seismic performance of the whole structure, thereby avoiding too large support stiffness in engineering practice. A nonlinear time-history analysis showed that lead rubber bearings (LRB) can reduce the support reaction to a certain extent and make it distribute uniformly, reducing the support design requirements under frequent earthquakes. During rare earthquakes, the LRB was basically in the plastic state and the support reaction remained near the yield force, which was reduced greatly compared with that of the original structure. The bearing hysteresis curve was full, while the plasticity development degree of the upper reticulated dome was greatly reduced and the elasticity was basically maintained, thus achieving a good damping effect

Clinical and genetic analysis of distal renal tubular acidosis in three Chinese children

Objective: Primary distal renal tubular acidosis (dRTA) is a rare genetic disease characterized by distal tubular dysfunction leading to metabolic acidosis and alkaline urine. Growth retardation is a major concern in these children. The disease is caused by defects in at least three genes (SLC4A1, ATP6V0A4, and ATP6V1B1) involved in urinary distal acidification. Several series of dRTA patients from different ethnic backgrounds have been genetically studied, but genetic studies regarding Chinese population is rare. Our aim was to investigate the clinical features and genetic basis of primary dRTA in Chinese children. Methods: Three unrelated patients with dRTA participated in our study. Next-generation sequencing was performed, and the findings were validated using the Sanger sequencing method. Results: All patients exhibited hyperchloraemic metabolic acidosis, abnormally high urine pH, hypokalemia, and nephrocalcinosis. Growth retardation was observed in all patients. During the follow-up (range 1–4 years), alkali replacement therapy corrected the systemic metabolic acidosis, and two patients demonstrated normal growth. rhGH therapy was administered to patient-3 at the age of 6 years, and his growth rate was significantly improved (growth velocity 9.6 cm/yr). In total, 5 mutations were identified in our cohort of three patients, and four mutations were novel. Conclusions: We report the clinical and molecular characteristics of dRTA patients from China. The four novel mutations detected in our study extend the spectrum of gene mutations associated with primary dRTA. Furthermore, our study confirms the effect of early treatment in improving growth for dRTA patient and provides insight into the effects of rhGH on dRTA patients who were diagnosed late and exhibiting a persistent growth delay despite appropriate therapy