ABSTRACT
Background
Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of kidney failure in children with phenotypic and genotypic heterogeneity. Our objective was to ...describe the genetic spectrum and identify the risk factors for kidney failure in children with CAKUT.
Methods
Clinical and genetic data were derived from a multicentre network Chinese Children Genetic Kidney Disease Database (CCGKDD) and the Chigene database. A total of 925 children with CAKUT who underwent genetic testing from 2014 to 2020 across China were studied. Data for a total of 584 children were obtained from the CCGKDD, including longitudinal data regarding kidney function. The risk factors for kidney failure were determined by the Kaplan–Meier method and Cox proportional hazards models.
Results
A genetic diagnosis was established in 96 of 925 (10.3%) children, including 72 (8%) with monogenic variants, 20 (2%) with copy number variants (CNVs) and 4 (0.4%) with major chromosomal anomalies. Patients with skeletal abnormalities were more likely to have large CNVs or abnormal karyotypes than monogenic variants. Eighty-two patients from the CCGKDD progressed to kidney failure at a median age of 13.0 years (95% confidence interval 12.4–13.6) and 24 were genetically diagnosed with variants of PAX2, TNXB, EYA1, HNF1B and GATA3 or the 48,XXYY karyotype. The multivariate analysis indicated that solitary kidney, posterior urethral valves, bilateral hypodysplasia, the presence of certain variants and premature birth were independent prognostic factors.
Conclusions
The genetic spectrum of CAKUT varies among different subphenotypes. The identified factors indicate areas that require special attention.
Graphical Abstract
Graphical Abstract
Schistosomiasis remains a major public health problem in China. The major endemic areas are located in the lake and marshland regions of southern China, particularly in areas along the middle and low ...reach of the Yangtze River. Spatial analytical techniques are often used in epidemiology to identify spatial clusters in disease regions. This study assesses the spatial distribution of schistosomiasis and explores high-risk regions in Hubei Province, China to provide guidance on schistosomiasis control in marshland regions.
In this study, spatial autocorrelation methodologies, including global Moran's I and local Getis-Ord statistics, were utilized to describe and map spatial clusters and areas where human Schistosoma japonicum infection is prevalent at the county level in Hubei province. In addition, linear logistic regression model was used to determine the characteristics of spatial autocorrelation with time.
The infection rates of S. japonicum decreased from 2009 to 2013. The global autocorrelation analysis results on the infection rate of S. japonicum for five years showed statistical significance (Moran's I > 0, P < 0.01), which suggested that spatial clusters were present in the distribution of S. japonicum infection from 2009 to 2013. Local autocorrelation analysis results showed that the number of highly aggregated areas ranged from eight to eleven within the five-year analysis period. The highly aggregated areas were mainly distributed in eight counties.
The spatial distribution of human S. japonicum infections did not exhibit a temporal change at the county level in Hubei Province. The risk factors that influence human S. japonicum transmission may not have changed after achieving the national criterion of infection control. The findings indicated that spatial-temporal surveillance of S. japonicum transmission plays a significant role on schistosomiasis control. Timely and integrated prevention should be continued, especially in the Yangtze River Basin of Jianghan Plain area.
The mobile edge computing (MEC) technology can provide mobile users (MU) with high reliability and low time-delay computing and communication services. The imbalanced edge cloud deployment can better ...adapt to the non-uniform spatial-time distribution of tasks and reduce the deployment cost of edge cloud servers. For multi-user and multi-task offloading decision based on the imbalanced edge cloud, a new offloading cost criteria, based on the tradeoff among time delay-energy consumption-cost, is designed to quantify the user experience of task offloading and to be the optimization target of offloading decision. Both the optimization problems of minimizing the sum offloading costs for all MUs (efficiency-based) and minimizing the maximal offloading cost per MU (fairness-based) are discussed. Efficiency-based offloading decision algorithm centralized greedy algorithm (CGA) and modified greedy algorithm (MGA) and fairness-based offloading decision algorithm fairness-based greedy algorithm (FGA) are proposed, respectively, and the performance bounds of the algorithm are analyzed. The simulation results show that the offloading cost of the MGA is lower than the CGA, the efficiency of resource utilization of the CGA is higher than that of the FGA, and the fairness of the FGA is stronger than that of the CGA.
Recently, diagnoses of radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) have become more common; prognosis is poor. It has been suggested that cancer stem cells account for ...radiotherapy resistance. By flow cytometry, different expression percents of CD133 and OCT4 in thyroid cancer cell lines were detected. By real-time quantitative PCR, different mRNA expression of CD133, OCT4, GLUT1, thyroglobulin (TG), thyroperoxidase (TPO) and sodium iodine symporter (NIS) was analyzed; the localization of CD133, OCT4, and NIS expression was examined using immunofluorescence confocal microscopy. Different expression of CD133, OCT4, and NIS in 21 human thyroid cancer and nodule tissues was investigated using immunohistochemistry. CD133-positive cells were isolated by magnetic sorting. Stronger colony formation ability of CD133-positive and weaker ability of CD133-negative cells in vivo were examined by colony formation. The effects of all-trans retinoic acid (ATRA) on CD133-positive cells in vivo were explored with Cell Counting Kit-8, colony formation, apoptosis, cell cycle, and ethynyl deoxyuridine assays. The ARO cell line and RAI-R DTC tissue specimens had more CD133-positive cells. NIS expression was significantly lower in RAI-R DTC tissue compared to radioiodine-sensitive DTC (RAI-DTC) tissue and specimens from patients with thyroid nodule. ATRA inhibited the stem cell characteristics of CD133-positive cells and induced CD133-positive cell differentiation to CD133-negative cells, and promoted CD133-positive cell apoptosis.
: The dry root of Sophora flavescens Ait. (SF) has long been used in a variety of Chinese herbal formulations to treat patients with cancer. Alkaloids are commonly known to present in SF as main ...active constituents. Here, we report that among the six characterized SF‐derived quinolizidine alkaloids including sophoridine, aloperine, sophocarpine, matrine, oxymatrine and cytisine, aloperine exerted the most potent in vitro cytotoxic activity against the human cancer cell lines and oxymatrine exhibited selective anti‐cancer activity against hepatocellular carcinoma HepG2 cells. Analysis of DNA fragmentation and PARP cleavage revealed that aloperine treatment for 48 hr induced apoptosis in HL‐60 cells. In addition, autophagic formation of acidic vacuole was also observed in HL‐60 cells exposed to aloperine. These results suggest that aloperine may be a novel contributor to the anti‐cancer properties of SF.
Abstract Lycorine is an alkaloid isolated from the bulb of the Amaryllidaceae Lycoris. Here, we report that treatment with lycorine resulted in survival inhibition and apoptosis induction in human ...leukemia cell lines. Lycorine induced apoptosis in human leukemia cells via intrinsic mitochondria pathway and caused a rapid-turnover of protein level of Mcl-1 which occurred before caspases activation. Furthermore, pronounced apoptosis accompanied by the down-regulation of Mcl-1 was also observed in blasts from patients with acute myeloid leukemia. Our findings suggest that lycorine may be a good candidate therapeutic agent against leukemia in worth of further evaluation.
A new multistimuli-responsive luminescent material, Cu8I8(4-dpda)6 n (1) (4-dpda=4-(diphenylphosphino)-N,N-dimethylaniline), has been obtained by combining inorganic Cu8I8 clusters and organic ...ligands 4-dpda, providing a novel in-/organic hybrid approach as an interesting alternative to all-organic approaches. Compound 1 responds well to thermo and mechanical force independently with color change due to the fact that the stimuli affect frontier molecular orbital and molecular packing modes, respectively.
In observational studies, statins have been suggested to have protective effects on venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). To this aim, we ...performed a two-sample mendelian randomization (MR) analysis to determine whether these associations were causal.
Data on the single nucleotide polymorphisms (SNPs) related to statin medication were obtained from the FinnGen study, and data for VTE, PE and DVT of lower extremities (LEDVT) were from the UK Biobank study, respectively. Inverse variance weighted (IVW) method was used as the principal analysis of MR, and sensitivity analysis was performed to detect horizontal pleiotropy and heterogeneity. MR estimates showed an inverse causal association between statin medication and the risk of VTE (odds ratio OR: 0.999, 95% CI: 0.998–1.000, P = 0.004), PE (OR: 0.999, 95% CI: 0.999–1.000, P = 0.011) and LEDVT (OR: 0.999, 95% CI: 0.999–1.000, P = 0.008).
Our findings provide direct evidence that statins might decrease the risk of VTE, PE and LEDVT in agreement with observational studies. The specific mechanism of statin therapy for venous thromboembolism needs to be further studied.
•Available evidence suggests that the effect of statins on venous thromboembolism outcomes remains inconclusive.•The Mendelian Randomization results showed that statin might decrease the risk of venous thromboembolism diseases.•This study provides evidence that statins have a protective effect on venous thromboembolism.
A sensor was proposed and experimentally demonstrated to improve temperature and pressure sensitivity by the Vernier effect. The sensor is composed of a cascaded Fabry-Perot interferometer (FPI) and ...a Sagnac interferometer (SI), which has almost the same free spectral range (FSR) forming the Vernier effect. The SI is a fiber-loop consisting of a segment of polarization maintaining fiber (PMF). The FPI consists of a section of quartz capillary inserted between two sections of single mode fiber. A micro-channel is drilled in the quartz capillary using a femtosecond laser to circulate air inside and outside the Fabry-Perot (F-P) cavity. SI and FPI in the sensor structure are selectively sensitive to temperature and pressure. In temperature sensing, the SI acts as the sensor and FPI as the reference, whereas in pressure measurements, the FPI is the sensing unit and SI the reference unit. Thus, in Vernier effect sensing, they perform the functions of reference or sensing units to each other. The sensor provides high sensitivity for both temperature and pressure. Experimental results show that the temperature sensitivity is ∼23.14 nm/°C, which is ∼13.4 times higher for the single SI sensor (-1.73 nm/°C), and the pressure sensitivity is ∼49.2 nm/MPa, which is ∼12.2 times higher than for the single FPI sensor (4.02 nm/MPa). The sensor has a simple structure, easy preparation, and high sensitivity of both temperature and gas pressure, and has widespread prospective application.
PDF
