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1.
Front Immunol ; 12: 657575, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33936087

RESUMEN

Immune checkpoint blockade (ICB) therapies have significantly improved the prognosis and shown considerable promise for cancer therapy; however, differences in ICB treatment efficacy between the elderly and young are unknown. We analyzed the studies enrolled in the meta-analysis using the deft approach, and found no difference in efficacy except melanoma patients receiving anti-PD-1 therapy. Similarly, higher treatment response rate and more favorable prognosis were observed in elderly patients in some cancer types (e.g., melanoma) with data from published ICB treatment clinical trials. In addition, we comprehensively compared immunotherapy-related molecular profiles between elderly and young patients from public trials and The Cancer Genome Atlas (TCGA), and validated these findings in several independent datasets. We discovered a divergent age-biased immune profiling, including the properties of tumors (e.g., tumor mutation load) and immune features (e.g., immune cells), in a pancancer setting across 27 cancer types. We believe that ICB treatment efficacy might vary depending on specific cancer types and be determined by both the tumor internal features and external immune microenvironment. Considering the high mutational properties in elderly patients in many cancer types, modulating immune function could be beneficial to immunotherapy in the elderly, which requires further investigation.

2.
Am J Ophthalmol ; 2021 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-33951445

RESUMEN

PURPOSE: To assess the prevalence of myelinated retinal nerve fibers (MRNFs), the rate of their change in a 10-year follow-up, and associations with ocular and systematic parameters in a population-based cohort. DESIGN: Longitudinal population-based cohort study. METHODS: The Beijing Eye study including 4439 participants aged 40+ years in 2001 and was repeated in 2011, with 2695 individuals (66.4% of the surviving) being re-examined in 2011. All participants underwent detailed physical and ocular examinations. MRNFs were diagnosed on fundus photographs and their change was assessed using a flicker method of fundus photographs. RESULTS: Out of 35 eyes (29 participants) with detected MRNFs at baseline (mean prevalence:0.4±0.26% per eye or 0.7%±0.41% per individual), 23 eyes from 20 individuals (17 (85%) participants with unilateral MRNFs) were re-examined in 2011. MRNF enlargement was detected in all 19 eyes (100%) with clear fundus photographs. The mean MRNF area increased from 4233±3670 µm2 (range:178-11643 µm2) at baseline to 5243±4092 µm2 (range:196-13297µm2) at follow-up (P<0.001), by 1010±1026 µm2 (18-3967 µm2) or by 47%±74% (9-315%). A larger MRNF increase was associated with an MRNF location distant from the optic disc as compared to a juxtapapillary location (P=0.001, standardized regression coefficient beta:-0.53), smaller MRNF area at baseline (P=0.006, beta:-0.34), and higher serum concentration of low-density lipoproteins (LDL) (P<0.001, beta:0.57). CONCLUSIONS: MRNFs (mean prevalence per eye:0.4%) showed, in association with higher LDL serum concentration and peripheral located MRNF, an enlargement during a 10-year follow-up, while in the same period no new MRNFs were detected in the total study cohort.

3.
Immunol Lett ; 2021 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-33951473

RESUMEN

Repeated exposure to fungi-contaminated dust can lead to multiple adverse effects on the lung, such as hypersensitivity pneumonitis, granuloma even irreversible fibrosis. 1,3-ß-glucan, a major cell wall component of fungi, is considered as its exposure biomarker. Existing studies showed that a series of Th responses were involved in 1,3-ß-glucan induced hypersensitivity pneumonitis, in which macrophages, Treg, and IL-10 producing B cells were reported to participate. The reciprocal interaction among those critical immune cells in 1,3-ß-glucan induced inflammation was not investigated yet. To clarify the regulatory mechanism of IL-10 producing B cells on Th and Treg, the current study set up a primary cell co-culture system. The anti-CD22 antibody was injected intraperitoneally to generate IL-10 producing B cells deficiency mouse model. Cells were isolated and purified from C57BL\6 mice in different groups. Flow cytometry was used to check the phenotype of different cell subtypes. CBA assay and real-time PCR were used to examine the levels of multiple cytokines. Our results indicated that IL-10 producing B cells could modulate the 1,3-ß-glucan induced inflammatory response. The modulation of IL-10 producing B cells on Th response after 1,3-ß-glucan treatment was cell contact independent. What's more, the modulation pattern of IL-10 producing B cells might be impaired without Treg response. IL-10-producing B cells regulated 1,3-ß-glucan induced Th responses in co-ordination with Treg cells.

5.
J Clin Microbiol ; 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33952598

RESUMEN

While China experienced a peak and decline in coronavirus disease 2019 (COVID-19) cases at the start of 2020, in subsequent months, regional outbreaks have continuously emerged. Resurgences of COVID-19 have also been observed in many other countries. In Guangzhou, China, a small outbreak, involving less than 100 residents, emerged in March and April 2020, and comprehensive and near-real-time genomic surveillance of SARS-CoV-2 was conducted. When the numbers of confirmed cases among overseas travelers increased, public health measures were enhanced by shifting from self-quarantine to central quarantine and SARS-CoV-2 testing for all overseas travelers. In an analysis of 109 imported cases, we found diverse viral variants distributed in the global viral phylogeny, which were frequently shared within households but not among passengers on the same flight. In contrast to the viral diversity of imported cases, local transmission was predominately attributed to two specific variants imported from Africa, including local cases that reported no direct or indirect contact with imported cases. The introduction events of the virus were identified or deduced before the enhanced measures were taken. These results show that the interventions were effective in containing the spread of SARS-CoV-2, and they ruled out the possibility of cryptic transmission of viral variants from the first wave in January and February 2020. Our study provides evidence and emphasizes the importance of controls for overseas travelers in the context of the pandemic and exemplifies how viral genomic data can facilitate COVID-19 surveillance and inform public health mitigation strategies.

6.
Artículo en Inglés | MEDLINE | ID: mdl-33955650

RESUMEN

Designing photo-responsive host-guest systems can provide versatile supramolecular tools for constructing smart systems and materials. Here we demonstrate the design of photo-responsive macrocyclic hosts, modulated by light-driven molecular rotary motors enabling switchable chiral guest recognition. The intramolecular cyclization of the two arms of a first-generation molecular motor with flexible oligoethylene glycol chains of different lengths resulted in crown-ether-like macrocycles with intrinsic motor function. As a result, the octaethylene glycol linkage enables the successful unidirectional rotation of molecular motors, simultaneously allowing the 1:1 host-guest interaction with ammonium salt guests. The binding affinity and stereoselectivity of the motorized macrocycle can be reversibly modulated, owing to the multi-state light-driven switching of geometry and helicity of the molecular motors. This approach provides an attractive strategy to construct stimuli-responsive host-guest systems and dynamic materials.

7.
Biomed Res Int ; 2021: 5524846, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33954172

RESUMEN

Suicidal behavior is a leading cause of death and often commences during adolescence/young adulthood (15~29 years old). The hippocampus, which consists of multiple functionally specialized subfields, may contribute to the pathophysiology of depression and suicidal behavior. We aimed to investigate the differences of hippocampal subfield volume between major depressive disorder (MDD) patients with and without suicide attempts and healthy controls in adolescents and young adults. A total of 40 MDD suicide attempters (MDD+SA), 27 MDD patients without suicide attempt (MDD-SA), and 37 healthy controls (HC) were recruited. High-resolution T1 MRI images were analyzed with the automated hippocampal substructure module in FreeSurfer 6.0. Volume differences among the groups were analyzed by a generalized linear model controlling for intracranial cavity volume (ICV). The relationship between hippocampal subfield volumes and clinical characteristics (HAM-D and SSI scores) was assessed using two-tailed partial correlation controlling for ICV in MDD+SA and MDD-SA. We found that MDD-SA had significantly smaller bilateral hippocampal fissure volume than HC and MDD+SA. No significant correlation was observed between hippocampal subfield volume and clinical characteristics (HAM-D and SSI scores) in MDD+SA and MDD-SA. Adolescent/young adult suicide attempters with MDD suicide attempters have larger bilateral hippocampal fissures than depressed patients without suicide attempts, independently from clinical characteristics. Within the heterogeneous syndrome of major depressive disorder that holds a risk for suicidality for subgroups, hippocampal morphology may help to explain or possibly predict such risk, yet longitudinal and functional studies are needed for understanding the biological mechanisms underlying.

9.
Cell Biol Int ; 2021 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-33945659

RESUMEN

The importance of flow shear stress (SS) on the differentiation of endothelial progenitor cells (EPCs) has been demonstrated in various studies. Cholesterol retention and miRNA regulation have been also proposed as relevant factors involved in this process, though evidence regarding their regulatory roles in the differentiation of EPCs is currently lacking. In the present study on high shear stress (HSS)-induced differentiation of EPCs, we investigated the importance of ABCA1, an important regulator in cholesterol efflux, and miR-25-5p, a potential regulator of endothelial reconstruction. We first revealed an inverse correlation between miR-25-5p and ABCA1 expression levels in EPCs under HSS treatment; their direct interaction was subsequently validated by a dual luciferase reporter assay. Further studies using flow cytometry and qPCR demonstrated that both miR-25-5p overexpression and ABCA1 inhibition led to elevated levels of specific markers of endothelial cells (ECs), with concomitant down-regulation of smooth muscle cell (SMC) markers. Finally, knockdown of ABCA1 in EPCs significantly promoted tube formation, which confirmed our conjecture. Our current results suggest that miR-25-5p might regulate the differentiation of EPCs partially through targeting ABCA1, and such a mechanism might account for HSS-induced differentiation of EPCs. This article is protected by copyright. All rights reserved.

10.
Sci Adv ; 7(18)2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33931457

RESUMEN

During the Mid-Miocene Climatic Optimum [MMCO, ~14 to 17 million years (Ma) ago], global temperatures were similar to predicted temperatures for the coming century. Limited megathermal paleoclimatic and fossil data are known from this period, despite its potential as an analog for future climate conditions. Here, we report a rich middle Miocene rainforest biome, the Zhangpu biota (~14.7 Ma ago), based on material preserved in amber and associated sedimentary rocks from southeastern China. The record shows that the mid-Miocene rainforest reached at least 24.2°N and was more widespread than previously estimated. Our results not only highlight the role of tropical rainforests acting as evolutionary museums for biodiversity at the generic level but also suggest that the MMCO probably strongly shaped the East Asian biota via the northern expansion of the megathermal rainforest biome. The Zhangpu biota provides an ideal snapshot for biodiversity redistribution during global warming.

11.
Cell Death Dis ; 12(5): 425, 2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33931585

RESUMEN

Serum deprivation-response protein (SDPR), a phosphatidylserine-binding protein, which is known to have a promising role in caveolar biogenesis and morphology. However, its function in hepatocellular carcinoma (HCC) was still largely unknown. In this study, we discussed the characterization and identification of SDPR, and to present it as a novel apoptosis candidate in the incidence of HCC. We identified 81 HCC cases with lower SDPR expression in the tumor tissues with the help of qRT-PCR assay, and lower SDPR expression was potentially associated with poor prognostication. The phenotypic assays revealed that cell proliferation, invasion, and migration were profoundly connected with SDPR, both in vivo and in vitro. The data obtained from the gene set enrichment analysis (GSEA) carried out on the liver hepatocellular carcinoma (LIHC), and also The Cancer Genome Atlas (TCGA) findings indicated that SDPR was involved in apoptosis and flow cytometry experiments further confirmed this. Furthermore, we identified the interaction between SDPR and apoptosis signal-regulating kinase 1 (ASK1), which facilitated the ASK1 N-terminus-mediated dimerization and increased ASK1-mediated signaling, thereby activating the JNK/p38 mitogen-activated protein kinases (MAPKs) and finally enhanced cell apoptosis. Overall, this work identified SDPR as a tumor suppressor, because it promoted apoptosis by activating ASK1-JNK/p38 MAPK pathways in HCC.

12.
J Diabetes Investig ; 2021 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-33943028

RESUMEN

AIMS: Non-alcoholic fatty liver disease and type 2 diabetes mellitus are closely related and often occur simultaneously in patients. Type 2 diabetes increases the risk of diabetic peripheral neuropathy, resulting in intolerable pain and extremity amputation that reduces the quality of life. However, the role of non-alcoholic fatty liver disease in the pathogenesis of diabetic peripheral neuropathy remains unclear. Thus, we evaluated the correlation of liver fibrosis and steatosis, which are representative histological morphologies of non-alcoholic fatty liver disease, with diabetic peripheral neuropathy in type 2 diabetes patients. RESULTS: Among the 520 patients, the prevalence of liver steatosis and fibrosis and diabetic peripheral neuropathy were 63.0% (n=328), 18.1% (n=94), and 52.1% (n=271), respectively. The prevalence of diabetic peripheral neuropathy was significantly elevated in patients with liver steatosis (55.7% vs. 44.9%, p=0.03) and fibrosis (61.5% vs. 50%, p=0.04), and it increased as liver stiffness measurement increased. Additionally, both hepatic steatosis (OR=1.48 [1.04-2.11], p=0.03) and fibrosis (OR=1.60 [1.02-2.51], p=0.04) were correlated with diabetic peripheral neuropathy. After adjusting for age, sex, weight, height, BMI, waist hip ratio, duration of T2DM, blood glucose, HOMA-IR, blood pressure, serum lipid, liver enzyme, urea, uric acid, creatinine, and inflammatory factors, liver fibrosis remained associated with diabetic peripheral neuropathy (OR=2.24 [1.11-4.53], p=0.02). CONCLUSION: The prevalence of diabetic peripheral neuropathy was elevated in patients with liver steatosis and fibrosis. Liver fibrosis was also independently associated with an increased risk of diabetic peripheral neuropathy.

13.
Sci Total Environ ; 786: 147434, 2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33964776

RESUMEN

Sertraline hydrochloride (Ser-HCl) is an effective and commonly used antidepressant drug, which is also frequently detected in aquatic environments. Our previous research showed that Ser-HCl changes the community composition of aquatic microbiome, but the understanding of the expression of functional pathways in microbial communities is still incomplete; to address this knowledge gap, we used meta-transcriptomics analysis to evaluate the toxicity of Ser-HCl to natural aquatic microbial communities cultured in laboratory microcosms. Meta-transcriptomic results show that a 15-day exposure to 50 µg/L Ser-HCl significantly changed the functional expression activity of aquatic microbial communities. Pathways related to lipid metabolism, energy metabolism, membrane transport function, and genetic information processing in the aquatic microbial community were severely inhibited under Ser-HCl treatment, but metabolism of cofactors and vitamins to alleviate biological toxicity after Ser-HCl exposure was enhanced. Our study thus reveals details of the effects of sertraline on the functioning of aquatic microbiome. Due to the extensive use of Ser-HCl and its strong biological activity, it should not continue to be an overlooked pollutant. Therefore, more attention should be paid to the negative effects of such biologically active drugs on the expression of aquatic microbiome.

14.
Chemosphere ; 280: 130770, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33971406

RESUMEN

The development of efficient, effective, and large-scale treatment methods to address high-risk emerging contaminants (ECs) is a growing challenge in environmental remediation. Herein, a novel parallel coupling strategy of adsorption separation and photodegradation regeneration (parallel ASPR) is proposed; subsequently, an adsorptive photocatalyst (Zn-doped BiOI) is designed to demonstrate how to effectively eliminate fluoroquinolones (FQs) from water with the proposed ASPR scheme. Compared with pure BiOI, the addition of Zn2+ during synthesis has a significant influence on the morphology and structure of the products, resulting in Zn-doped BiOI samples with up to 5 times the specific surface area, 32 times the adsorption capacity, and 20 times the photocurrent intensity. The optimized Zn-doped BiOI sample has an excellent adsorption efficiency for FQs with a removal rate that exceeds 95% after 5 min of adsorption for all 6 tested FQ antibiotics. Then the adsorbed contaminants can be effectively degraded during the later visible-light irradiation process, and the adsorbent can be regenerated synchronously, showing excellent ASPR cycling performances. The mechanisms of rapid adsorption and photocatalysis were explored via material characterizations, adsorption models, density functional theory calculations, and photogenerated species analyses. The results reveal that the enhanced adsorption of Zn-doped BiOI for FQs is due to its high specific surface area, coordination-based chemical adsorption, and surface electrostatic attraction, while its superior visible-light photodegradation performance is mainly ascribed to its strong redox ability, abundant surface oxygen vacancies, and enhanced photogenerated carrier separation efficiency.

15.
Orphanet J Rare Dis ; 16(1): 212, 2021 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-33971920

RESUMEN

BACKGROUND: Acid sphingomyelinase deficiency (ASMD) (also known as Niemann-Pick disease types A and B) is a rare and debilitating lysosomal storage disorder. This prospective, multi-center, multinational longitudinal study aimed to characterize the clinical features of chronic forms of ASMD and disease burden over time in children and adults. RESULTS: Fifty-nine patients (31 males/28 females) ranging in age from 7 to 64 years with chronic ASMD types A/B and B and at least two disease symptoms participated from 5 countries. Disease characteristics were assessed at baseline, after 1 year, and at the final visit (ranging from 4.5 to 11 years). Thirty patients (51%) were < 18 years at baseline (median age 12 years), and 29 were adults (median age 32 years). Overall, 32/59 patients completed the final visit, 9 died, 9 discontinued, and 9 were lost to follow up. Common clinical characteristics that tended to worsen gradually with time were splenomegaly, hepatomegaly, interstitial lung disease, lung diffusion capacity (DLCO), and dyslipidemia. Spleen volumes ranged from 4 to 29 multiples of normal at baseline, and splenomegaly was moderate or severe in 86%, 83%, and 90% of individuals at baseline, year 1, and final visits, respectively. The proportion of all individuals with interstitial lung disease was 66% (39/59) at baseline and 78% (25/32) at the final visit, while median % predicted DLCO decreased by > 10% from baseline to the final visit. Nine patients died (15%), eight of causes related to ASMD (most commonly pneumonia); of these eight patients, five (63%) had symptom onset at or before age 2. Overall, six of the nine deaths occurred before age 50 with three occurring before age 20. Individuals with either severe splenomegaly or prior splenectomy were ten times more likely to have died during the follow-up period than those with smaller or intact spleens (odds ratio 10.29, 95% CI 1.7, 62.7). Most children had growth deficits that persisted into adulthood. CONCLUSIONS: This study provides important information about the natural history of chronic ASMD and provides a longitudinal view of the spectrum of disease manifestations and major morbidities in children and adults and supports the selection of clinically meaningful endpoints in therapeutic trials.

16.
Support Care Cancer ; 2021 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-33973079

RESUMEN

BACKGROUND: Increasing evidence indicates that nutritional status could influence the survival of cancer patients. This study aims to develop and validate a nomogram with nutrition-related parameters for predicting the overall survival of cancer patients. PATIENTS AND METHODS: A total of 8749 patients from the multicentre cohort study in China were included as the primary cohort to develop the nomogram, and 696 of these patients were recruited as a validation cohort. Patients' nutritional status were assessed using the PG-SGA. LASSO regression models and Cox regression analysis were used for factor selection and nomogram development. The nomogram was then evaluated for its effectiveness in discrimination, calibration, and clinical usefulness by the C-index, calibration curves, and decision curve analysis. Kaplan-Meier survival curves were used to compare the survival rate. RESULTS: Seven independent prognostic factors were identified and integrated into the nomogram. The C-index was 0.73 (95% CI, 0.72 to 0.74) and 0.77 (95% CI, 0.74 to 0.81) for the primary cohort and validation cohort, which were both higher than 0.59 (95% CI, 0.58 to 0.61) of the TNM staging system. DCA demonstrated that the nomogram was higher than the TNM staging system and the TNM staging system combined with PG-SGA. Significantly median overall survival differences were found by stratifying patients into different risk groups (score < 18.5 and ≥ 18.5) for each TNM category (all Ps < 0.001). CONCLUSION: Our study screened out seven independent prognostic factors and successfully generated an easy-to-use nomogram, and validated and shown a better predictive validity for the overall survival of cancer patients.

17.
Sci Rep ; 11(1): 8428, 2021 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-33875714

RESUMEN

This prospective study aimed to introduce the application of the multiplanar fracture redactor (MFR) in the treatment of tibial shaft fractures with intramedullary nails (IMNs). From February to June 2018, a total of 18 patients with tibial shaft fractures were recruited. MFR was used to help achieve the reduction of tibial shaft fractures with IMN in all patients. The demographic and fracture characteristics, surgical data, postoperative complications and prognostic indicators of 16 patients were recorded. All operations were performed under closed reduction, excellent radiological and functional outcomes were observed. The average duration of surgery, intraoperative blood loss, intraoperative fluoroscopy times, number of intraoperative assistants, and duration of postoperative hospital stay were 91.2 ± 26.1 min, 95.0 ± 58.3 ml, 19.2 ± 2.3 times, 1 (1-2), and 7.8 ± 2.6 days, respectively. The mean Lysholm Knee Function Score (LKFS), American Orthopaedic Foot and Ankle Society (AOFAS) and visual analogue scale (VAS) scores at one year after surgery were 96.8 ± 2.1, 94.8 ± 2.9, and 1 (0-3), respectively. Wound infection, non-union, malunion or complications associated with MFR were not observed in this study. Thus, MFR was a safe and neater method to achieve and maintain the reduction of tibial shaft fractures with IMN.

18.
Z Naturforsch C J Biosci ; 76(5-6): 187-192, 2021 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-33909958

RESUMEN

Alzheimer's disease (AD) is a common neurodegenerative disease with high morbidity among elderly people. A genetic attribution has been extensively proved. Here, we propose to further prioritize genes that harbor single nucleotide variation (SNV) or structural variation (SV) for AD and explore the underlying potential mechanisms through exploiting their expression and methylation spectra. A high-confidence AD-associated candidate gene list was obtained from the ClinVar and Human Gene Mutation Database (HGMD). Genome-wide methylation and expression profiles of AD and normal subjects were downloaded from the Gene Expression Omnibus (GEO). Through comprehensive comparison of expression and methylation levels between AD and normal samples, as well as different stages of AD samples, SORL1 was identified as the most plausible gene for AD incidence and progression. Gene Set Enrichment Analysis (GSEA) revealed significant activation of the ABC (ATP binding cassette) transporter with the aberrant up-regulation of SORL1 within AD samples. This study unfolds the expression and methylation spectra of previously probed genes with SNV or SV in AD for the first time, and reports an aberrant activation of the ABC transporter pathway that might contribute to AD progression. This should shed some light on AD diagnosis and precision treatment.

19.
Cell Death Dis ; 12(4): 393, 2021 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-33846290

RESUMEN

Cardiac septum malformations account for the largest proportion in congenital heart defects. The transcription factor Sox7 has critical functions in the vascular development and angiogenesis. It is unclear whether Sox7 also contributes to cardiac septation development. We identified a de novo 8p23.1 deletion with Sox7 haploinsufficiency in an atrioventricular septal defect (AVSD) patient using whole exome sequencing in 100 AVSD patients. Then, multiple Sox7 conditional loss-of-function mice models were generated to explore the role of Sox7 in atrioventricular cushion development. Sox7 deficiency mice embryos exhibited partial AVSD and impaired endothelial to mesenchymal transition (EndMT). Transcriptome analysis revealed BMP signaling pathway was significantly downregulated in Sox7 deficiency atrioventricular cushions. Mechanistically, Sox7 deficiency reduced the expressions of Bmp2 in atrioventricular canal myocardium and Wnt4 in endocardium, and Sox7 binds to Wnt4 and Bmp2 directly. Furthermore, WNT4 or BMP2 protein could partially rescue the impaired EndMT process caused by Sox7 deficiency, and inhibition of BMP2 by Noggin could attenuate the effect of WNT4 protein. In summary, our findings identify Sox7 as a novel AVSD pathogenic candidate gene, and it can regulate the EndMT involved in atrioventricular cushion morphogenesis through Wnt4-Bmp2 signaling. This study contributes new strategies to the diagnosis and treatment of congenital heart defects.

20.
Med Sci Monit ; 27: e930513, 2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33859156

RESUMEN

BACKGROUND Regional citrate anticoagulation (RCA) is a recommended anticoagulation alternative for patients at high risk of bleeding while undergoing intermittent hemodialysis. Previous reports implied the risk of citrate application on bone metabolism. It is unclear whether long-term use of RCA is safe for maintenance hemodialysis patients in terms of bone metabolism. MATERIAL AND METHODS Seven patients with cerebral hemorrhage were included in the study. Blood samples were collected at baseline and 4 and 8 weeks after treatment. Spent dialysate samples were collected during each mid-week dialysis session, using the partial dialysate collection method. All patients were treated with RCA for 4 to 8 weeks, according to their clinical condition. We assessed bone metabolism-associated parameters, bone turnover markers, and magnesium loss at each dialysis session. RESULTS Serum magnesium levels were 1.24±0.13 mmol/L at baseline and significantly decreased to 1.16±0.14 mmol/L after 4 weeks of RCA treatment (P=0.025). Most patients had negative magnesium balance during citrate hemodialysis. Serum total calcium levels did not change significantly after treatment. One bone marker, N-terminal propeptide of type I procollagen (PINP), significantly decreased from 146.07±130.12 mmol/L to 92.42±79.01 mmol/L after citrate treatment (P=0.018). No significant changes were detected in other bone turnover markers. CONCLUSIONS Relatively long-term RCA treatment may decrease serum magnesium levels due to negative magnesium balance. Bone formation marker PINP seemed to decrease after treatment, while other bone turnover markers did not change significantly. Further investigation is needed to verify the effect of RCA on bone remodeling.

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