Poor-Grade Aneurysmal Subarachnoid Hemorrhage: Diagnosis, Therapeutical Management, and Prognosis

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological condition and these patients often have unfavorable outcomes at the long-term follow-up. Poor-grade aSAH is a severe subtype of aSAH and is defined as World Federation of Neurosurgical Surgeon (WFNS) grade IV or V. All patients should be treated by a multidisciplinary team that consists of vascular neurosurgeons, interventional neuroradiologists, neurologists, and anesthetists. Aneurysm rebleeding occurs in the poor-grade aSAH within the first 72 h after ictus. Timing of treatment for aSAH has shifted from delayed to early treatment of ruptured aneurysms, and there will be a trend toward early or ultra-early treatment for poor-grade aSAH. However, there is no consensus regarding the optimal timing of treatment for poor-grade aSAH. Endovascular coiling has provided a viable alternative to surgical clipping. An increasing number of patients have received endovascular treatment. There are limited data on high-level clinical trials focused on the treatment of poor-grade aSAH. An accurate prediction model remains challenging. Predicting long-term outcome is essential to support treatment decision-making. We reviewed the current therapeutical management and prognosis of poor-grade aSAH

Characterization of suspended sand concentrations in the Yangtze River Estuary and adjacent waters

IntroductionThe study on the distribution characteristics of suspended sediment concentration (SSC) in estuaries is an important subject in the study of estuaries and coasts, which has important theoretical significance and practical value.MethodsIn order to fully understand the characteristics of SSC in the Yangtze River Estuary and its adjacent waters, this paper uses fixed vertical observation data and navigation type large area observation data as data sources to analyze the distribution characteristics of SSC in the Yangtze River Estuary and its adjacent waters under different tidal current states and its vertical profile characteristics. It discusses the impact of tidal current velocity on SSC and the changes of SSC in the Yangtze River Estuary and its adjacent waters from 2018 to 2020. And the applicability of the Rouse and Soulsby formulas in the Yangtze River Estuary and its adjacent waters was verified.ResultsIt was found that the Rouse and Soulsby models have high applicability in the study area, and the prediction accuracy based on the Li’s Soulsby model is higher. This study provides effective support for carrying out marine forecasting, analysis and evaluation, and provides theoretical basis for carrying out analysis of the current situation of estuarine mudflat resources and prediction of the evolution trend. It plays an important role in scientific and comprehensive research and management of mudflat resources in Shanghai.DiscussionHowever, this study only explored the characteristic patterns of SSC in the Yangtze River Estuary and its adjacent waters based on field observations, but SSC is a more complex water environment parameter that is influenced by a variety of factors. The effects of salinity, temperature and wind speed should be considered in subsequent studies

TRAF6 Promotes Myogenic Differentiation via the TAK1/p38 Mitogen-Activated Protein Kinase and Akt Pathways

p38 mitogen-activated protein kinase (MAPK) is an essential kinase involved in myogenic differentiation. Although many substrates of p38 MAPK have been identified, little is known about its upstream activators during myogenic differentiation. TRAF6 is known to function in cytokine signaling during inflammatory responses. However, not much is known about its role in myogenic differentiation and muscle regeneration. We showed here that TRAF6 and its intrinsic ubiquitin E3 ligase activity are required for myogenic differentiation. In mouse myoblasts, knockdown of TRAF6 compromised the p38 MAPK and Akt pathways, while deliberate activation of either pathway rescued the differentiation defect caused by TRAF6 knockdown. TAK1 acted as a key signal transducer downstream of TRAF6 in myogenic differentiation. In vivo, knockdown of TRAF6 in mouse muscles compromised the injury-induced muscle regeneration without impairing macrophage infiltration and myoblast proliferation. Collectively, we demonstrated that TRAF6 promotes myogenic differentiation and muscle regeneration via the TAK1/p38 MAPK and Akt pathways

Polysaccharides from the root of Angelica sinensis promotes hematopoiesis and thrombopoiesis through the PI3K/AKT pathway

<p>Abstract</p> <p>Background</p> <p>Dozens of Traditional Chinese Medicine (TCM) formulas have been used for promotion of "blood production" for centuries, and we are interested in developing novel thrombopoietic medicines from these TCMs. Our previous studies have demonstrated the hematopoietic effects of DangGui BuXue Tong (DBT), a formula composed of <it>Radix Angelicae Sinensis </it>and <it>Radix Astragali </it>in animal and cellular models. As a step further to identify and characterize the active chemical components of DBT, we tested the hematopoietic and particularly, thrombopoietic effects of polysaccharide-enriched fractions from the root of <it>Radix Angelicae Sinensis </it>(APS) in this study.</p> <p>Methods</p> <p>A myelosuppression mouse model was treated with APS (10 mg/kg/day). Peripheral blood cells from APS, thrombopoietin and vehicle-treated samples were then counted at different time-points. Using the colony-forming unit (CFU) assays, we determined the effects of APS on the proliferation and differentiation of hematopoietic stem/progenitor cells and megakaryocytic lineages. Using a megakaryocytic cell line M-07e as model, we analyzed the cellular apoptosis progression with and without APS treatment by Annexin V, Mitochondrial Membrane Potential and Caspase 3 assays. Last, the anti-apoptotic effect of APS on cells treated with Ly294002, a Phosphatidylinositol 3-Kinse inhibitor (PI3K) was also tested.</p> <p>Results</p> <p>In animal models, APS significantly enhanced not only the recovery of platelets, other blood cells and their progenitor cells, but also the formation of Colony Forming Unit (CFU). In M-07e cells, we observed the anti-apoptotic effect of APS. Treatment by Ly294002 alone increased the percentage of cells undergoing apoptosis. However, addition of APS to Ly294002-treated cells significantly reduced the percentage of cells undergoing apoptosis.</p> <p>Conclusions</p> <p>APS promotes hematopoiesis and thrombopoiesis in the mouse model. This effect likely resulted from the anti-apoptosis activity of APS and is likely to involve the PI3K/AKT pathway.</p

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Function of SOX7 in normal hematopoiesis and in acute lymphoblastic leukemia

The SOX (Sry-related HMG box) genes belong to a family of transcription factors containing a High-Mobility-Group box domain. In an initial screen, SOX7 was uniquely down-regulated in myeloid malignancies compared with most cases of precursor B-cell acute lymphoblastic leukemia (ALL) and normal bone marrow cell, leading us to examine the expression and function of SOX7 during normal hematopoietic differentiation and in acute lymphoblastic leukemia. By studying human umbilical cord blood (UCB), SOX7 expression in different hematopoietic lineages was evaluated by RT-PCR. SOX7 was preferentially expressed in CD34+CD38- compared with CD34+CD38+ population and in CD34-CD19+ compared with CD34-CD33+ cells. SOX7 expression was down-regulated in colonies in CFU assay and in engrafting myeloid cells in NOD/SCID mouse transplantation. Transfecting SOX7 siRNA into CD34+ cells reduced cell growth and the CD34+CD33+ population in 3-day culture; induced cell-cycle arrest at G1 phase; reduced clonogenic activities but had no effect on apoptosis. Overall engraftment into NOD/SCID mice were not affected but the engrafting myeloid populations were reduced. In acute lymphoblastic leukemia, SOX7 was robustly expressed, compared with that in normal UCB and acute myeloid leukemia (AML). In 5 ALL patients in whom the coding sequence of SOX7 was examined, 3 of them showed mutations (amino acid change) in the SOX C-terminal transactivation domain. No mutation was observed in the β-catenin binding site. Knockdown of SOX7 with specific siRNA significantly increased appoptosis and decreased cell proliferation. SOX7 knockdown by shRNA in a precursor B-cell ALL cell line Nalm20 significantly reduced its engraftment into NOD/SCID mice. In summary, SOX7 is preferentially expressed in early hematopoietic stem and progenitor cells and is important for the maintenance of myeloid progenitor. It is also expressed in the primitive population of ALL and is important for leukemia initiation in ALL. The present study has generated important information about the regulation of normal hematopoiesis and acute lymphoblastic leukemiapublished_or_final_versionMedicineDoctoralDoctor of Philosoph