Objective
Functional vein end to arterial side (ETS) anastomosis uses vein side to arterial side (STS) anastomosis with distal vein ligation, which can achieve similar effects as those of ETS after ...STS anastomosis. The purpose of the study was to provide a meta-analysis to compare the clinical outcomes between traditional and functional ETS anastomosis in radiocephalic fistula for dialysis access.
Methods
Databases including PubMed, EMbase, the Cochrane Library, CNKI, Wanfang database were searched from the inception to February 6, 2020. Eligible studies comparing traditional and functional ETS anastomosis in radiocephalic fistula were included. Data were analyzed using Review Manager Version 5.3.
Results
Seven studies were included in the meta-analysis. Five randomized controlled trials and two cohort studies involving 841 patients were identified. Compared with traditional ETS anastomosis, functional ETS anastomosis had shorter anastomosis time (MD − 9.54, 95% CI − 17.96 to − 1.12,
P
= 0.03), higher surgical success rate (OR 3.80, 95% CI 1.76–8.22,
P
< 0.01), fewer complications(OR 0.18, 95% CI 0.08–0.39,
P
< 0.01), higher patency rate after 3 months (OR 4.91, 95% CI 1.19–20.33,
P
= 0.03), higher patency rate after 6 months (OR 1.90, 95%CI 1.09–3.31,
P
= 0.02), higher patency rate after 12 months (OR 1.70, 95% CI 1.09–2.66,
P
= 0.02). There was no difference after the two arteriovenous (AVF) anastomosisl methods concerning AVF maturation time (SMD − 0.48, 95% CI − 1.30–0.34,
P
= 0.25) and patency rate after 1 month (OR 1.77, 95% CI 0.65–4.80,
P
= 0.26).
Conclusion
Functional ETS anastomosis had advantages of easy operation, high surgical success rate, few complications, high patency rate of 3 months and long-term, but did not have obvious advantage in the early stages concerning AVF maturation time and 1-month patency rate.
Explaining the wetting mechanism of Cu–P brazing materials and Cu remains challenging. This fundamental research aims to reveal the wettability mechanism of Si, Sn, and Zr doping on the interfacial ...bond strength of the Cu3P/Cu system through the first principles study. We carried out several sets of calculations to test the validity of the result; included in the work are those used to establish the interfacial structure and to analyze the effect of doping on the wettability. Specific analysis was carried out in terms of three aspects: the work of adhesion (Wad), the charge density difference, and the density of states (DOS). The calculated results show that doping with Si, Sn, and Zr elements can effectively improve the wettability within the CuP/Cu interface with very high accuracy, and is particularly effective when doped with Zr. These results provide an insightful theoretical guide for enhancing the CuP/Cu system’s wettability by adding active elements.
Endoscopic parathyroidectomy(EPTX) has been gradually introduced as a minimally invasive treatment for refractory secondary hyperparathyroidism (SHPT). However, it is uncertain about the efficacy and ...safety compared between EPTX and open parathyroidectomy (OPTX) for refractory SHPT.
This meta-analysis was conducted to evaluate the efficacy and safety of EPTX and OPTX for secondary hyperp arathyroidism (SHPT).
Databases including PubMed, EMbase, Cochrane Library, CNKI, and Wanfang were searched. Eligible studies comparing EPTX and OPTX for refractory SHPT were included.
Compared with OPTX, EPTX has the shorter hospital stay (p < 0.01) and lower incidences of hoarseness or recurrent laryngeal nerve injury (p = 0.04). There was no significant difference between EPTX and OPTX concerning operation time (p = 0.49), intraoperative blood loss (p = 0.24), postoperative parathyroid hormone levels (p = 0.22), postoperative calcium levels (p = 0.93), postoperative phosphorus levels (p = 0.37), and complications including neck ecchymosis (p = 0.87), subcutaneous haematoma (p = 0.18), and wound infection (p = 0.11).
EPTX and OPTX are both effective methods for refractory SHPT. EPTX had the shorter hospital stay and lower incidences of hoarseness or recurrent laryngeal nerve injury.
Pathophysiological conditions causing mitochondrial dysfunction and altered transmembrane potential (∆ψm) initiate a mitochondrial respiratory stress response, also known as mitochondrial retrograde ...response, in a variety of mammalian cells. An increase in the cytosolic Ca2+ Ca2+c as part of this signaling cascade activates Ca2+ responsive phosphatase, calcineurin (Cn). Activation of IGF1R accompanied by increased glycolysis, invasiveness, and resistance to apoptosis is a phenotypic hallmark of C2C12 skeletal muscle cells subjected to this stress. The signaling is associated with activation and increased nuclear translocation of a number of transcription factors including a novel NFκB (cRel:p50) pathway, NFAT, CREB and C/EBPδ. This culminates in the upregulation of a number of nuclear genes including Cathepsin L, RyR1, Glut4 and Akt1. We observed that stress regulated transcription activation of nuclear genes involves a cooperative interplay between NFκB (cRel:p50), C/EBPδ, CREB, and NFAT. Our results show that the functional synergy of these factors requires the stress-activated heterogeneous nuclear ribonucleoprotein, hnRNPA2 as a transcriptional coactivator. We report here that mitochondrial stress leads to induced expression and activation of serine threonine kinase Akt1. Interestingly, we observe that Akt1 phosphorylates hnRNPA2 under mitochondrial stress conditions, which is a crucial step for the recruitment of this coactivator to the stress target promoters and culmination in mitochondrial stress-mediated transcription activation of target genes. We propose that mitochondrial stress plays an important role in tumor progression and emergence of invasive phenotypes.
A number of studies show that mitochondrial DNA (mtDNA) depletion and attendant activation of retrograde signaling induces tumor progression. We have reported previously that activation of a novel ...nuclear factor-Kappa B pathway is critical for the propagation of mitochondrial retrograde signaling, which induces both phenotypic and morphological changes in C2C12 myoblasts and A549 lung carcinoma cells. In this study, we investigated the role of stress-induced nuclear factor-Kappa B in tumor progression in xenotransplanted mice. We used a retroviral system for the inducible expression of small interfering RNA against IkBα and IkBβ mRNAs. Expression of small interfering RNA against IkBβ markedly impaired tumor growth and invasive ability of mtDNA-depleted C2C12 myoblasts and also thwarted anchorage-independent growth of the cells. Knockdown of IkBα mRNA, however, did not have any modulatory effect in this cell system. Moreover, expression of small interfering RNA against IkBβ reduced the expression of marker genes for retrograde signaling and tumor growth in xenografts of mtDNA-depleted cells. Our findings demonstrate that IkBβ is a master regulator of mitochondrial retrograde signaling pathway and that the retrograde signaling plays a role in tumor growth in vivo. In this regard, IkBβ supports the tumorigenic potential of mtDNA-depleted C2C12 cells.
Prolactin receptors (PRLr) expressed in a majority of breast cancer are activated by prolactin and growth hormone. The PRLr is commonly stabilized in human breast cancer due to decreased ...phosphorylation of residue Ser(349), which, when phosphorylated, recruits the beta Trcp E3 ubiquitin ligase and facilitates PRLr degradation. Here, we show that constitutive oncogenic signaling downstream of ErbB2 and Ras stabilizes PRLr via inhibitory phosphorylation of glycogen synthase kinase-3beta (GSK3 beta) on Ser(9). Importantly, inactivation of GSK3 beta correlates with elevated levels of PRLr protein in clinical human breast cancer specimens. Additional studies using pharmacologic, biochemical, and genetic approaches reveal that GSK3 beta is a bona fide PRLr kinase that phosphorylates PRLr on Ser(349) and is required for the recognition of PRLr by beta Trcp, as well as for PRLr ubiquitination and degradation.
Understanding the nature of streamflow response to precipitation inputs is at the core of hydrological applications and water resource management. Indices such as the base flow index, recession ...constant, and response lag of a watershed retain an important place in hydrology as metrics to compare watersheds and understand the impact of human activity, geology, geomorphology, soils, and climate on precipitation–runoff relations. Extracting characteristics of the hyetograph–hydrograph relationship is often done manually, which is time consuming and may result in subjective and potentially inconsistent outcomes. Here, we present a MATLAB‐based toolbox, called HydRun, for rapid and flexible rainfall–runoff analysis. HydRun uses a series of flexible routines to extract base flow from the hydrograph and then computes commonly used time instants of the rainfall–runoff relationship. HydRun provides users the flexibility to decide thresholds and limits of analysis, but objectively computes hydrometric indices. The toolkit includes a graphical user interface and example files. In this paper, we apply HydRun to 4 watersheds, 3 in Scotland and 1 in Canada, to demonstrate the software functions and highlight important decisions the user must make in its application.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxic side product formed in the chemical synthesis of desmethylprodine opioid analgesic, which induces Parkinson disease. Monoamine ...oxidase B, present in the mitochondrial outer membrane of glial cells, catalyzes the oxidation of MPTP to the toxic 1-methyl-4-phenylpyridinium ion (MPP+), which then targets the dopaminergic neurons causing neuronal death. Here, we demonstrate that mitochondrion-targeted human cytochrome P450 2D6 (CYP2D6), supported by mitochondrial adrenodoxin and adrenodoxin reductase, can efficiently catalyze the metabolism of MPTP to MPP+, as shown with purified enzymes and also in cells expressing mitochondrial CYP2D6. Neuro-2A cells stably expressing predominantly mitochondrion-targeted CYP2D6 were more sensitive to MPTP-mediated mitochondrial respiratory dysfunction and complex I inhibition than cells expressing predominantly endoplasmic reticulum-targeted CYP2D6. Mitochondrial CYP2D6 expressing Neuro-2A cells produced higher levels of reactive oxygen species and showed abnormal mitochondrial structures. MPTP treatment also induced mitochondrial translocation of an autophagic marker, Parkin, and a mitochondrial fission marker, Drp1, in differentiated neurons expressing mitochondrial CYP2D6. MPTP-mediated toxicity in primary dopaminergic neurons was attenuated by CYP2D6 inhibitor, quinidine, and also partly by monoamine oxidase B inhibitors deprenyl and pargyline. These studies show for the first time that dopaminergic neurons expressing mitochondrial CYP2D6 are fully capable of activating the pro-neurotoxin MPTP and inducing neuronal damage, which is effectively prevented by the CYP2D6 inhibitor quinidine.
Background: Metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to toxic MPP+ is critical in chemically induced Parkinson disease.
Results: Mitochondrial CYP2D6 supported by adrenodoxin/adrenodoxin reductase efficiently catalyzed MPTP to MPP+.
Conclusion: Mitochondria from dopaminergic neurons contain the enzymes for the metabolism of MPTP to MPP+.
Significance: This is a new pathway for the metabolism of MPTP to toxic MPP+ within the dopaminergic neurons.
Flow regimes are critical for determining physical and biological processes in rivers and their classification and regionalization traditionally seeks to link patterns of flow to physiographic, ...climate and other information. There are many approaches to, and rationales for, catchment classification, with those focused on streamflow often seeking to relate a particular response characteristic to a physical property or climatic driver. Rationales include such topics as prediction in ungauged basins (PUB), and providing guidance for model selection in poorly understood hydrological systems. The annual daily hydrograph (ADH) is a first‐order easily visualized integrated expression of catchment function, and over many years the average ADH is a distinct hydrological signature that differentiate catchments from each other. In this study, we use t‐SNE, a state‐of‐the‐art technique of dimensionality reduction, to classify 17 110 ADHs for 304 reference catchments in mountainous Western North America. t‐SNE is chosen over other conventional methods of dimensionality reduction (e.g., PCA) as it presents greater separability of ADHs, which are projected on a 2D map where the similarities are evaluated according to their map distance. We then utilize a Deep Learning encoder to upgrade the non‐parametric t‐SNE to a parametric approach, enhancing its capability to address ‘unseen’ samples. Results showed that t‐SNE successfully clustered ADHs of similar flow regimes on the 2D map and allowed more accurate classification with KNN. In addition, many compact clusters on the 2D map in the coastal Pacific Northwest suggest information redundancy in the local streamflow network. The t‐SNE map provides an intuitive way to visualize the similarity of high‐dimensional data of ADHs, groups catchments with like characteristics, and avoids the reliance on subjective hydrometric indicators.
t‐SNE converts Annual Daily Hydrographs (ADHs) into a 2D map, where ADHs from different western North American flow regimes show distinct clusters. This provides an intuitive way to visualize and compare the similarity among a large number of hydrographs. Incorporating a Deep Learning encoder, we provide a convenient tool to project new hydrographs on to the map, identify similar counterparts and establish the flow regime for any given ADH.