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1.
Neuroimage ; 210: 116584, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32004717

RESUMO

Diffusion Magnetic Resonance Imaging (dMRI) has shown great potential in probing tissue microstructure and structural connectivity in the brain but is often limited by the lengthy scan time needed to sample the diffusion profile by acquiring multiple diffusion weighted images (DWIs). Although parallel imaging technique has improved the speed of dMRI acquisition, attaining high resolution three dimensional (3D) dMRI on preclinical MRI systems remained still time consuming. In this paper, kernel principal component analysis, a machine learning approach, was employed to estimate the correlation among DWIs. We demonstrated the feasibility of such correlation estimation from low-resolution training DWIs and used the correlation as a constraint to reconstruct high-resolution DWIs from highly under-sampled k-space data, which significantly reduced the scan time. Using full k-space 3D dMRI data of post-mortem mouse brains, we retrospectively compared the performance of the so-called kernel low rank (KLR) method with a conventional compressed sensing (CS) method in terms of image quality and ability to resolve complex fiber orientations and connectivity. The results demonstrated that the KLR-CS method outperformed the conventional CS method for acceleration factors up to 8 and was likely to enhance our ability to investigate brain microstructure and connectivity using high-resolution 3D dMRI.

2.
Chem Commun (Camb) ; 56(14): 2210, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32031562

RESUMO

Correction for 'One-pot construction of functionalized aziridines and maleimides via a novel pseudo-Knoevenagel cascade reaction' by Jie Lei et al., Chem. Commun., 2020, DOI: .

3.
J Plant Physiol ; 246-247: 153132, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32062292

RESUMO

Studies have shown that pathogenic bacteria infections induce the overproduction of reactive oxygen species (ROS) in plants. Cyanide-resistant respiration, an energy-dissipating pathway in plants, has also been induced by a pathogenic bacteria infection. However, it is unknown whether the induction of cyanide-resistant respiration under the pathogenic bacteria infection was caused by ROS. In this study, two pathogenic Erwinia strains were used to infect potato tuber, and membrane lipid peroxidation levels and the cyanide-resistant respiration capacity were determined. In addition, StAOX expression and regulation by ROS in potato tuber were analyzed. Moreover, the role of the Ca2+ pathway in regulating cyanide-resistant respiration was determined. The results showed that ROS induced cyanide-resistant respiration in potato tuber infected by Erwinia. Cyanide-resistant respiration inhibited the production of H2O2. Intracellular Ca2+ regulated the expression of calcium-dependent protein kinase (StCDPK1, StCDPK4, and StCDPK5) in potato, which indirectly controlled intracellular ROS levels. These results indicate that Ca2+ metabolism is involved in ROS-induced cyanide-resistant respiration.

4.
Mol Plant ; 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32017998

RESUMO

Improved soybean cultivars have been adapted to grow at a wide range of latitudes, enabling expansion of cultivation worldwide. However, the genetic basis for this broad adaptation is still not clear. Here we report the identification of GmPRR3b as a major flowering time regulatory gene that has been selected during domestication and genetic improvement for geographic expansion. Through genome-wide association study (GWAS) of a diverse landrace panel of soybean (comprised of 279 accessions), we identified 16 candidate quantitative loci associated with flowering time and maturity time. The strongest signal resides on the known flowering gene E2, verify the effectiveness of our approach. We detected strong association signals of a genomic region containing GmPRR3b with both flowering and maturity time. Haplotype analysis revealed that GmPRR3bH6 is the major form that has been utilized during recent breeding of modern cultivars. mRNA profiling analysis showed that GmPRR3bH6 displays a rhythmic and photoperiod-dependent expression that is preferentially induced under long day conditions. Overexpression of GmPRR3bH6 conferred increased main stem node number and high yield phenotypes, while knockout of GmPRR3bH6 by CRISPR-Cas9 technology retarded growth and delayed floral transition. GmPRR3bH6 appears to act as a transcriptional repressor of multiple predicted circadian clock genes, including GmCCA1a which directly upregulates J/GmELF3a to modulate flowering time. Taken together, the causal SNP (Chr12:5520945) likely endows GmPRR3bH6 a moderate but appropriate activity, which is associated with early flowering and vigorous growth traits preferentially selected for broad adaption in landraces and improved cultivars.

5.
Biochemistry ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32022543

RESUMO

Transition state analogue inhibitor design (TSID) and fragment-based drug design (FBDD) are drug design approaches typically used independently. Methylthio-DADMe-Immucillin-A (MTDIA) is a tight-binding transition state analogue of bacterial 5'-methylthioadenosine nucleosidases (MTANs). Previously, Salmonella enterica MTAN structures were found to bind MTDIA and ethylene glycol fragments, but MTDIA modified to contain similar fragments did not enhance affinity. Seventy-five published MTAN structures were analyzed, and co-crystallization fragments were found that might enhance the binding of MTDIA to other bacterial MTANs through contacts external to MTDIA binding. The fragment-modified MTDIAs were tested with Helicobacter pylori MTAN and Staphylococcus aureus MTANs (HpMTAN and SaMTAN) as test cases to explore inhibitor optimization by potential contacts beyond the transition state contacts. Replacement of a methyl group with a 2'-ethoxyethanol group in MTDIA improved the dissociation constant 14-fold (0.09 nM vs 1.25 nM) for HpMTAN and 81-fold for SaMTAN (0.096 nM vs 7.8 nM). TSID combined with FBDD can be useful in enhancing already powerful inhibitors.

6.
Reprod Sci ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-32046435

RESUMO

Considerable efforts have been invested to elucidate the potential mechanisms involved in the physiopathology of endometriosis. However, to date, prior research has not been conclusive. This research has examined one particular mechanism, i.e., the effect of ADAR1 on endometriosis lesions. Eutopic endometrium was collected from women with (n = 25) and without endometriosis (n = 25), respectively. The expression of ADAR1 mRNA was measured based on quantitative real-time polymerase chain reactions (RT-qPCR). Both Western blot and immunohistochemistry were performed to establish ADAR1 protein expression levels. The results indicated that ADAR1 mRNA and proteins were significantly greater in the eutopic endometrium of the women with endometriosis, compared to the women without (P < 0.05). The Cell Counting Kit-8 (CCK-8) and EdU method were conducted to examine the effect of ADAR1 on cell viability and proliferation in eutopic endometriosis cells. A transwell assay was also used to detect the role of ADAR1 in the invasion of endometrial cells. The results obtained showed that ADAR1 promoted endometrial cell viability, proliferation, and invasion (P < 0.05). This informed our conclusion that the ADAR1 gene is upregulated in endometriosis, potentially paying a pivotal role in the physiopathology of endometriosis.

7.
Plant Biol (Stuttg) ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32052535

RESUMO

The cyanide-resistant respiration that occurs in potato mitochondria is one of the important pathways for energy dissipation. It can be activated by glare. However, it is unclear what roles cyanide-resistant respiration play in the high-light stress of potatoes. This study designed a CRISPR vector for the functional gene StAOX of the potato cyanide-resistant respiratory. Agrobacterium tumefaciens GV3101 was transformed into potato. H2 O2 level, MDA content, antioxidant activity and Cyanide-resistant respiratory capacity of potato leaves under high light stress were determined. Photosynthetic efficiency and chlorophyll content were determined. In addition, the operation of the malate-oxaloacetate shuttle route and the transcription level of photorespiration related enzymes were also examined. The results showed that two base substitutions occurred at the sequencing target site on the leaves of a transformed potato. Accumulation of active oxygen and the increase of membrane lipid peroxidation were detected in the transformed potato leaves. Lower photosynthetic efficiency was observed. The transcription level of the malate-oxaloacetate shuttle route and photorespiration-related enzymes were also significantly increased. These results indicated that cyanide-resistant respiration is an important physiological process in the potato against high light stress. It also suggested that the plant cyanide-resistant respiration is closely related to photosynthesis. It implies the unexplored importance of plant cyanide-resistant respiration to plant photosynthesis, energy conversion, and carbon skeleton formation.

8.
Semin Cancer Biol ; 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32014608

RESUMO

Strictly regulated protein degradation by ubiquitin-proteasome system (UPS) is essential for various cellular processes whose dysregulation is linked to serious diseases including cancer. Skp2, a well characterized component of Skp2-SCF E3 ligase complex, is able to conjugate both K48-linked ubiquitin chains and K63-linked ubiquitin chains on its diverse substrates, inducing proteasome mediated proteolysis or modulating the function of tagged substrates respectively. Overexpression of Skp2 is observed in various human cancers associated with poor survival and adverse therapeutic outcomes, which in turn suggests that Skp2 engages in tumorigenic activity. To that end, the oncogenic properties of Skp2 are demonstrated by various genetic mouse models, highlighting the potential of Skp2 as a target for tackling cancer. In this article, we will describe the downstream substrates of Skp2 as well as upstream regulators for Skp2-SCF complex activity. We will further summarize the comprehensive oncogenic functions of Skp2 while describing diverse strategies and therapeutic platforms currently available for developing Skp2 inhibitors.

9.
Chem Commun (Camb) ; 56(14): 2194-2197, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31971170

RESUMO

An Ugi, novel pseudo-Knoevenagel, ring expansion cascade reaction was discovered and utilized for the synthesis of aziridinyl succinimides in one-pot. Subsequently, densely functionalized aziridines and maleimides have been designed and synthesized through similar cascade reactions. The target compounds were prepared by means of a mild reaction and a simple operation procedure, which could be applicable to a broad scope of starting materials. This series of novel cascade reactions generates opportunities for the tailored synthesis of a wide range of biologically active scaffolds through tuneable Ugi inputs. Discovery of compound 8i with comparable potency to sorafenib in liver cancer cell lines could provide a new avenue for liver cancer drug discovery.

10.
Blood Purif ; : 1-10, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31940611

RESUMO

OBJECTIVES: This study aimed to examine the association of serum sodium with infection-related mortality and its age difference among continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: A total of 1,656 CAPD patients from January 2006 to December 2013 were included in this study. All patients were followed up until December 2018. Hyponatremia was defined as serum sodium <135 mmol/L. Cox proportional hazards regression model was used to investigate the relationship between baseline serum sodium levels and infection-related mortality. RESULTS: Participants were aged 47.5 ± 15.3 years, 666 (40.2%) patients were female. Glomerulonephritis was the main cause of end-stage renal disease (61.1%). After a median of 46 months of follow-up, 507 patients died. Among the deaths, 252 (49.7%) died from cardiovascular diseases, 105 (20.7%) from infections, and 150 (29.6%) from other causes. The overall infection-related mortality was 14.8 events per 1,000 patients-year, which was higher in patients aged ≥50 years than those younger than 50 years (28.3 vs. 5.3 events per 1,000 patients-year). In the entire cohort, hyponatremia at was not associated with infection-related (hazards ratios [HR] 1.66, 95% CI 0.91-3.02) and all-cause mortality (HR 1.14, 95% CI 0.83-1.57) after adjusting for potential confounders. There was a significant interaction by age of association of serum sodium with infection-related (p = 0.002) and all-cause (p = 0.0002) death. Age-stratified analysis showed that compared with control group, hyponatremia was independently related to increased risks of infection-related death, but not all-cause mortality in patients aged ≥50 years, with HR of 2.32 (95% CI 1.25-4.32) and 1.33 (95% CI 0.95-1.87), respectively. CONCLUSIONS: Hyponatremia was associated with increased risk of infection-related mortality in CAPD patients aged ≥50 years.

11.
Elife ; 92020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31916937

RESUMO

Immune factors in snails of the genus Biomphalaria are critical for combating Schistosoma mansoni, the predominant cause of human intestinal schistosomiasis. Independently, many of these factors play an important role in, but do not fully define, the compatibility between the model snail B. glabrata, and S. mansoni. Here, we demonstrate association between four previously characterized humoral immune molecules; BgFREP3, BgTEP1, BgFREP2 and Biomphalysin. We also identify unique immune determinants in the plasma of S. mansoni-resistant B. glabrata that associate with the incompatible phenotype. These factors coordinate to initiate haemocyte-mediated destruction of S. mansoni sporocysts via production of reactive oxygen species. The inclusion of BgFREP2 in a BgFREP3-initiated complex that also includes BgTEP1 almost completely explains resistance to S. mansoni in this model. Our study unifies many independent lines of investigation to provide a more comprehensive understanding of the snail immune system in the context of infection by this important human parasite.

12.
J Med Chem ; 63(2): 441-469, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31550151

RESUMO

Chirality is important in drug discovery because stereoselective drugs can ameliorate therapeutic difficulties including adverse toxicity and poor pharmacokinetic profiles. The human kinome, a major druggable enzyme class has been exploited to treat a wide range of diseases. However, many kinase inhibitors are planar and overlap in chemical space, which leads to selectivity and toxicity issues. By exploring chirality within the kinome, a new iteration of kinase inhibitors is being developed to better utilize the three-dimensional nature of the kinase active site. Exploration into novel chemical space, in turn, will also improve drug solubility and pharmacokinetic profiles. This perspective explores the role of chirality to improve kinome druggability and will serve as a resource for pioneering kinase inhibitor development to address current therapeutic needs.

13.
Epigenetics ; 15(1-2): 199-214, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31314649

RESUMO

Precision toxicology evaluates the toxicity of certain substances by isolating a small group of cells with a typical phenotype of interest followed by a single cell sequencing-based analysis. In this in vitro attempt, ochratoxin A (OTA), a typical mycotoxin and food contaminant, is found to induce G0/G1 phase cell cycle arrest in human renal proximal tubular HKC cells at a concentration of 20 µM after a 24h-treatment. A small number of G0/G1 phase HKC cells are evaluated in both the presence and absence of OTA. These cells are sorted with a flow cytometer and subjected to mRNA and DNA methylation sequencing using Smart-Seq2 and single-cell reduced-representation bisulfite sequencing (scRRBS) technology, respectively. Integrated analysis of the transcriptome and methylome profiles reveals that OTA causes abnormal expression of the essential genes that regulate G1/S phase transition, act as signal transductors in G1 DNA damage checkpoints, and associate with the anaphase-promoting complex/cyclosome. The alteration of their DNA methylation status is a significant underlying epigenetic mechanism. Furthermore, Notch signaling and Ras/MAPK/CREB pathways are found to be suppressed by OTA. This attempt at precision toxicology paves the way for a deeper understanding of OTA toxicity and provides an innovative strategy to researchers in the toxicology and pharmacology field.

14.
Environ Int ; 134: 105284, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707300

RESUMO

BACKGROUND: Perfluorinated compounds (PFCs) were reported to result in the endocrine disruption by activating the estrogen receptor (ER) and inducing ER-mediated transcriptions. OBJECTIVE: The aim of the present work was to perform cross-species comparisons on the characteristics of eight PFCs binding to humans ERα and to rats ERα. METHODS: In the present work, in vivo tests, including serum estradiol level assay and immunohistochemical staining, fluorescence assay and molecular models were applied. RESULTS: Based on the in vivo experiments, the exposure of PFOA and PFOS to female rats was proved to increase the ERα expression in the terus, suggesting that PFCs may act as estrogenic compounds to activate ERα in vivo. The further fluorescence assay presented that these eight PFCs have stronger binding abilities to human ERα than to rat ERα. In addition, the differences in binding specificities between human ERα and rat ERα were identified in the process of molecular dynamics modeling with the term of helix position and the ability of coregulator recruitment. It can be found that more and stronger charge clamps could form between PFCs with human ERα than with rat ERα. Also, the eight PFCs presented lower binding energies in human ERα systems, which proved that eight PFCs presented much stronger binding abilities with human ERα. DISCUSSION: In all, it can be concluded that PFCs might be more sensitive to human ERα than to that of rats, which also suggested the greater susceptibility to adverse effects on humans. The present work was a beginning assessment of a cross-species comparison, providing important information on health impacts of PFCs in humans.

15.
Sci China Life Sci ; 63(1): 59-67, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31872378

RESUMO

The zebrafish has become a popular vertebrate animal model in biomedical research. However, it is still challenging to make conditional gene knockout (CKO) models in zebrafish due to the low efficiency of homologous recombination (HR). Here we report an efficient non-HR-based method for generating zebrafish carrying a CKO and knockin (KI) switch (zCKOIS) coupled with dual-color fluorescent reporters. Using this strategy, we generated hey2zKOIS which served as a hey2 KI reporter with EGFP expression. Upon Cre induction in targeted cells, the hey2zCKOIS was switched to a non-functional CKO allele hey2zCKOIS-invassociated with TagRFP expression, enabling visualization of the CKO alleles. Thus, simplification of the design, and the visibility and combination of both CKO and KI alleles make our zCKOIS strategy an applicable CKO approach for zebrafish.

16.
J Environ Sci (China) ; 86: 154-163, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31787180

RESUMO

Previous studies have reported associations of short-term exposure to different sources of ambient fine particulate matter (PM2.5) and increased mortality or hospitalizations for respiratory diseases. Few studies, however, have focused on the short-term effects of source-specific PM2.5 on emergency room visits (ERVs) of respiratory diseases. Source apportionment for PM2.5 was performed with Positive Matrix Factorization (PMF) and generalized additive model was applied to estimate associations between source-specific PM2.5 and respiratory disease ERVs. The association of PM2.5 and total respiratory ERVs was found on lag4 (RR = 1.011, 95%CI: 1.002, 1.020) per interquartile range (76 µg/m3) increase. We found PM2.5 to be significantly associated with asthma, bronchitis and chronic obstructive pulmonary disease (COPD) ERVs, with the strongest effects on lag5 (RR = 1.072, 95%CI: 1.024, 1.119), lag4 (RR = 1.104, 95%CI: 1.032, 1.176) and lag3 (RR = 1.091, 95%CI: 1.047, 1.135), respectively. The estimated effects of PM2.5 changed little after adjusting for different air pollutants. Six primary PM2.5 sources were identified using PMF analysis, including dust/soil (6.7%), industry emission (4.5%), secondary aerosols (30.3%), metal processing (3.2%), coal combustion (37.5%) and traffic-related source (17.8%). Some of the sources were identified to have effects on ERVs of total respiratory diseases (dust/soil, secondary aerosols, metal processing, coal combustion and traffic-related source), bronchitis ERVs (dust/soil) and COPD ERVs (traffic-related source, industry emission and secondary aerosols). Different sources of PM2.5 contribute to increased risk of respiratory ERVs to different extents, which may provide potential implications for the decision making of air quality related policies, rational emission control and public health welfare.


Assuntos
Poluição do Ar/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Material Particulado/análise , Doenças Respiratórias/epidemiologia , Serviço Hospitalar de Emergência , Humanos
17.
Cell Death Dis ; 10(12): 950, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831728

RESUMO

As a new class of non-coding RNA, circular RNAs (circRNAs) play crucial roles in the development and progression of various cancers. However, the detailed functions of circRNAs in cervical cancer have seldom been reported. In this study, circRNA sequence was applied to detect the differentially expressed circRNAs between cervical cancer tissues and adjacent normal tissues. The relationships between circCLK3 level with clinicopathological characteristics and prognosis were analyzed. In vitro CCK-8, cell count, cell colony, cell wound healing, transwell migration and invasion, and in vivo tumorigenesis and lung metastasis models were performed to evaluate the functions of circCLK3. The pull-down, RNA immunoprecipitation (RIP), luciferase reporter and rescue assays were employed to clarify the interaction between circCLK3 and miR-320a and the regulation of miR-320a on FoxM1. We found that the level of circCLK3 was remarkably higher in cervical cancer tissues than in adjacent normal tissues, and closely associated with tumor differentiation, FIGO stage and depth of stromal invasion. Down-regulated circCLK3 evidently inhibited cell growth and metastasis of cervical cancer in vitro and in vivo, while up-regulated circCLK3 significantly promoted cell growth and metastasis in vitro and in vivo. The pull-down, luciferase reporter and RIP assays demonstrated that circCLK3 directly bound to and sponge miR-320a. MiR-320a suppressed the expression of FoxM1 through directly binding to 3'UTR of FoxM1 mRNA. In addition, FoxM1 promoted cell proliferation, migration, and invasion of cervical cancer, while miR-320a suppressed cell proliferation, migration, and invasion through suppressing FoxM1, and circCLK3 enhanced cell proliferation, migration and invasion through sponging miR-320a and promoting FoxM1 expression. In summary, circCLK3 may serve as a novel diagnostic biomarker for disease progression and a promising molecular target for early diagnoses and treatments of cervical cancer.

18.
AAPS J ; 22(1): 14, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31853739

RESUMO

Aurora kinase B (AKB), a Ser/Thr kinase that plays a crucial role in mitosis, is overexpressed in several cancers. Clinical inhibitors targeting AKB bind to the active DFG "in" conformation of the kinase. It would be beneficial, however, to understand if AKB is susceptible to type II kinase inhibitors that bind to the inactive, DFG "out" conformation, since type II inhibitors achieve higher kinome selectivity and higher potency in vivo. The DFG "out" conformation of AKB is not yet experimentally determined which makes the design of type II inhibitors exceedingly difficult. An alternate approach is to simulate the DFG "out" conformation from the experimentally determined DFG "in" conformation using atomistic molecular dynamics (MD) simulation. In this work, we employed metadynamics (MTD) approach to simulate the DFG "out" conformation of AKB by choosing the appropriate collective variables. We examined structural changes during the DFG-flip and determined the interactions crucial to stabilize the kinase in active and inactive states. Interestingly, the MTD approach also identified a unique transition state (DFG "up"), which can be targeted by small molecule inhibitors. Structural insights about these conformations is essential for structure-guided design of next-generation AKB inhibitors. This work also emphasizes the usefulness of MTD simulations in predicting macromolecular conformational changes at reduced computational costs.

19.
Gastroenterol Res Pract ; 2019: 6704673, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781196

RESUMO

Background and Aims: Liver fibrosis blood tests, platelet count/spleen diameter ratio (PSR), and contrast-enhanced CT are diagnostic alternatives for gastroesophageal varices, but they have heterogeneous diagnostic performance among different study populations. Our study is aimed at evaluating their diagnostic accuracy for esophageal varices (EVs) and gastric varices (GVs) in cirrhotic patients with and without previous endoscopic variceal therapy. Methods: Patients with liver cirrhosis who underwent blood tests and contrast-enhanced CT scans as well as endoscopic surveillance should be potentially eligible. EVs needing treatment (EVNTs) and GVs needing treatment (GVNTs) were recorded according to the endoscopic results. Area under the curves (AUCs) were calculated. Results: Overall, 279 patients were included. In 175 patients without previous endoscopic variceal therapy, including primary prophylaxis population (n = 70), acute bleeding population (n = 38), and previous bleeding population (n = 67), the diagnostic accuracy of contrast-enhanced CT for EVNTs was higher (AUCs = 0.816-0.876) as compared to blood tests and PSR; by comparison, the diagnostic accuracy of contrast-enhanced CT for GVNTs was statistically significant among primary prophylaxis population (AUC = 0.731, P = 0.0316), but not acute or previous bleeding population. In 104 patients with previous endoscopic variceal therapy (i.e., secondary prophylaxis population), contrast-enhanced CT was the only statistically significant alternative for diagnosing EVNTs and GVNTs but with modest accuracy (AUCs = 0.673 and 0.661, respectively). Conclusions: Contrast-enhanced CT might be a diagnostic alternative for EVNTs in cirrhotic patients, but its diagnostic performance was slightly weakened in secondary prophylaxis population. Additionally, contrast-enhanced CT may be considered for diagnosis of GVNTs in primary prophylaxis population without previous endoscopic variceal therapy and secondary prophylaxis population.

20.
J Nephrol ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31773639

RESUMO

BACKGROUND: Elevated serum phosphorus level is a risk factor for progression of chronic kidney disease in non-dialysis patients. However, the association of serum phosphorus level with residual renal function (RRF) loss among incident continuous ambulatory peritoneal dialysis (CAPD) patients remains unclear. METHODS: We performed a retrospective analysis of prospectively collected cohort of 1245 incident CAPD patients from January 2006 to December 2015 and followed up until December 2017. Patients were stratified into tertiles according to baseline serum phosphorus levels. RRF loss was defined as residual glomerular filtration rate (mL/min/1.73 m2) reaching zero or estimated urine output less than 200 mL/day on two successive clinic visits. Propensity-score matched Cox's proportional hazards and competing risk models were performed to examine the association of serum phosphorus with RRF loss. RESULTS: A total of 421 (33.82%) patients had loss of RRF over a median follow-up of 26.23 months. In the entire cohort, elevated serum phosphorus was associated with increased risk for RRF loss after adjustment. In the propensity-score matched cohort, patients in the 3rd tertile of serum phosphorus had a 51% higher risk of RRF loss than those in the combination of the 1st and 2nd tertiles. Furthermore, the association of serum phosphorus level with RRF loss differed by sex (interaction P = 0.018). The adjusted HRs per 1 mg/dL increase in serum phosphorus level of RRF loss were 1.32 (95% CI 1.15-1.50, P < 0.001) for male and 1.03 (95% CI 0.87-1.21, P = 0.750) for female, respectively. These findings persisted in competing risk analysis. CONCLUSION: Higher serum phosphorus levels independently predicts RRF loss in men treated with CAPD.

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