PSTPIP2 Inhibits the Inflammatory Response and Proliferation of Fibroblast-Like Synoviocytes in vitro

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease and its pathogenesis remains unclear. Fibroblast-like synoviocytes (FLSs) play an important role in the pathogenesis of RA. Proline-serine-threonine phosphatase interacting protein 2 (PSTPIP2) is an adaptor protein, which is associated with auto-inflammatory disease. In this study, we selected adjuvant-induced arthritis (AIA) as animal model to study the role of PSTPIP2 in FLSs. We found that the expression of PSTPIP2 was significantly down-regulated in synovial tissues and FLSs of AIA rat compared with normal group. And overexpression of PSTPIP2 could inhibit the proliferation and inflammatory response of FLSs. Moreover, the proliferation and inflammatory response of FLSs were promoted with PSTPIP2 silencing treatment. In terms of mechanism, we found that the expression of PSTPIP2 was closely related to NF-κB signaling pathway. Overall, our results suggested that PSTPIP2 inhibits the proliferation and inflammatory response of FLSs, which might be closely related to NF-κB signaling pathway

Multiple evaluations, risk assessment, and source identification of heavy metals in surface water and sediment of the Golmud River, northeastern Qinghai-Tibet Plateau, China

The water quality of the Golmud River is essential for environmental preservation and economic growth of Golmud city and Qarhan Salt Lake in China. Thirty-four samples of surface water and sediment from seventeen places in the Golmud River and thirty-two dustfall samples in the Qaidam Basin were collected. The concentrations of heavy metals (HMs) were measured; water quality, risk assessment, and multiple source analysis were applied. Concentrations of HMs in water were Zn > Cu > Ni > As > Pb > Cd > Hg, and in sediment were Ni > Zn > Pb > As > Cu > Cd > Hg. In water, the Nemerow pollution index (NP) values indicated that most of the sampling points seemly were seriously polluted; other water quality assessment results suggested no pollution. In sediment, the concentrations of 27% HMs exceeded the background values of soil in Qinghai; 48% exceeded the Earth crust background values, which were As, Hg, and Cd. The single factor index method (Pi), geological accumulation index (Igeo), and contamination factor (CF) revealed that As pollution is serious, followed by Hg and Cd; the pollution load index (PLI) and modified pollution index (mCd) values indicated that 64% and 57% of samples were polluted. NP values are shown serious pollution. The ecological risk results demonstrated a low risk in water and a medium risk in sediment. The average total hazard quotient values in sediment and water for adults and children revealed low non-carcinogenic risks. Carcinogenic risk indicated Ni in water and sediment, and As in sediment may be involved in cancer risk. Multivariate statistics showed that the HMs mainly came from nature, and human activities will also impact them. The upper continental crust values indicated that As and Hg have high background values. The saline dust storm was one of the essential sources of HMs, especially Hg. Various provenances constituted the material cycling of HMs in the surface environment

p53/p21 Pathway Involved in Mediating Cellular Senescence of Bone Marrow-Derived Mesenchymal Stem Cells from Systemic Lupus Erythematosus Patients

Our and other groups have found that bone marrow-derived mesenchymal stem cells (BM-MSCs) from systemic lupus erythematosus (SLE) patients exhibited senescent behavior and are involved in the pathogenesis of SLE. Numerous studies have shown that activation of the p53/p21 pathway inhibits the proliferation of BM-MSCs. The aim of this study was to determine whether p53/p21 pathway is involved in regulating the aging of BM-MSCs from SLE patients and the underlying mechanisms. We further confirmed that BM-MSCs from SLE patients showed characteristics of senescence. The expressions of p53 and p21 were significantly increased, whereas levels of Cyclin E, cyclin-dependent kinase-2, and phosphorylation of retinoblastoma protein were decreased in the BM-MSCs from SLE patients and knockdown of p21 expression reversed the senescent features of BM-MSCs from SLE patients. Our results demonstrated that p53/p21 pathway played an important role in the senescence process of BM-MSCs from SLE

Comparison of out-of-plane short axis with in-plane long axis for ultrasound-guided radial arterial cannulation: A systematic review with trial sequential analysis of randomised controlled trials

BackgroundIt is controversial whether the short-axis out-of-plane or long-axis in-plane approach is a better needling technique for ultrasound-guidance radial artery cannulation. We aimed to compare the efficacy and safety of the two approaches for ultrasound-guided radial artery cannulation.MethodsA systematic search of Medline, Embase, the Cochrane Library, and Web of Science for relevant articles published until 1 May 2021 was conducted. Randomised controlled trials comparing the long-axis in-plane with short-axis out-of-plane approaches were included. Review Manager software version 5.4, STATA version 14.2, and trial sequential analysis (TSA) version 0.9.5.10 Beta were used for statistical analysis. Risk of bias and methodological quality of all studies included in this review were assessed according to the Cochrane Collaboration tool for the risk of bias. Subgroup analyses and meta-regression were performed to explore sources of heterogeneity.ResultsThe rate of cannula insertion success on the first attempt was similar between the short-axis out-of-plane and long-axis in-plane approaches (RR = 1.03; 95% CI: 0.83 to 1.28; P = 0.79; I2 = 83.0%). No significant differences were observed in total time to successful cannulation between the two approaches (MD = –3.9; 95% CI:-18.30 to 10.49; P = 0.6; I2 = 97%). However, the required information size for the success rate of the first attempt and total time to successful cannulation was not reached.ConclusionIt remains inconclusive whether short-axis out-of-plane is a better choice for radial arterial cannulation than the long-axis in-plane approach. Inexperienced operators may need more attempts and longer ultrasound location time with the short-axis out-of-plane technique.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021236098]

Autoimmune nodopathy with anti-contactin 1 antibody characterized by cerebellar dysarthria: a case report and literature review

BackgroundAutoimmune nodopathy (AN) has emerged as a novel diagnostic category that is pathologically different from classic chronic inflammatory demyelinating polyneuropathy. Clinical manifestations of AN include sensory or motor neuropathies, sensory ataxia, tremor, and cranial nerve involvement. AN with a serum-positive contactin-1 (CNTN1) antibody usually results in peripheral nerve demyelination. In this study, we reported a rare case of AN with CNTN1 antibodies characterized by the presence of CNTN1 antibodies in both serum and cerebrospinal fluid, which is associated with cerebellar dysarthria.MethodsA 25-year-old man was admitted to our hospital due to progressive dysarthria with limb tremors. The patient was initially diagnosed with peripheral neuropathy at a local hospital. Three years after onset, he was admitted to our hospital due to dysarthria, apparent limb tremor, and limb weakness. At that time, he was diagnosed with spinocerebellar ataxia. Eight years post-onset, during his second admission, his condition had notably deteriorated. His dysarthria had evolved to typical distinctive cerebellar characteristics, such as tremor, loud voice, stress, and interrupted articulation. Additionally, he experienced further progression in limb weakness and developed muscle atrophy in the distal limbs. Magnetic resonance imaging (MRI), nerve conduction studies (NCS), and autoimmune antibody tests were performed.ResultsThe results of the NCS suggested severe demyelination and even axonal damage to the peripheral nerves. MRI scans revealed diffuse thickening of bilateral cervical nerve roots, lumbosacral nerve roots, cauda equina nerve, and multiple intercostal nerve root sheath cysts. Furthermore, anti-CNTN1 antibody titers were 1:10 in the cerebrospinal fluid (CSF) and 1:100 in the serum. After one round of rituximab treatment, the patient showed significant improvement in limb weakness and dysarthria, and the CSF antibodies turned negative.ConclusionApart from peripheral neuropathies, cerebellar dysarthria (central nervous system involvement) should not be ignored in AN patients with CNTN1 antibodies

Safety and effects of a home-based Tai Chi exercise rehabilitation program in patients with chronic heart failure: study protocol for a randomized controlled trial

IntroductionChronic heart failure (CHF), as the final stage of the progression of many cardiovascular disorders, is one of the main causes of hospitalization and death in the elderly and has a substantial impact on patients' quality of life (QOL). Exercise-based cardiac rehabilitation (CR) has been shown to considerably enhance QOL and prognosis. Given the barriers to center-based CR faced by most developing countries in the form of expensive instruments, the development of home-based CR is necessary. Tai Chi, as an instrument-free exercise, has been shown to be successful in treating elderly CHF individuals. Fu Yang, as one of the academic concept of Traditional Chinese Medicine (TCM), believes that the fundamental pathogenesis of CHF is the gradual decline of Yang, and emphasizes the restoration of Yang physiological function in the treatment process. Therefore, we develope a home-based Tai Chi exercise rehabilitation program called Fu Yang Tai Chi (FYTC) for elderly CHF patients by combining the Fu Yang Theory of TCM with the CR theory. The objective of this study is to evaluate the effectiveness, acceptability, and safety of the program.Methods and analysisWe suggest conducting a parallel randomized controlled clinical trial with open label. Eighty CHF elderly participants will be randomly assigned in a 1:1 ratio to the FYTC rehabilitation program group or the moderate-intensity aerobic walking control group. Eligible participants will engage in either three sessions weekly of FYTC or walking exercise for 12 weeks. The primary outcome is the relative change in 6 min walk distance (6MWD). The secondary outcomes are the plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), QOL, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), self-rating anxiety scale (SAS) and depression scale (SDS), exercise skills, and noninvasive hemodynamic monitoring. Throughout the trial, adverse events will be recorded for safety evaluation. Researchers who are blinded to the treatment allocation will analyze the data.Ethics and disseminationThis research was authorized by the Guang'anmen Hospital Ethics Committee of the Chinese Academy of Medical Sciences (2022-141-KY). Our findings will be shared online and in academic conferences as well as in peer-reviewed journals. Trial registration numberChiCTR2200063511

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

Semi-Supervised Learning for Seismic Impedance Inversion Using Generative Adversarial Networks

Seismic impedance inversion is essential to characterize hydrocarbon reservoir and detect fluids in field of geophysics. However, it is nonlinear and ill-posed due to unknown seismic wavelet, observed data band limitation and noise, but it also requires a forward operator that characterizes physical relation between measured data and model parameters. Deep learning methods have been successfully applied to solve geophysical inversion problems recently. It can obtain results with higher resolution compared to traditional inversion methods, but its performance often not fully explored for the lack of adequate labeled data (i.e., well logs) in training process. To alleviate this problem, we propose a semi-supervised learning workflow based on generative adversarial network (GAN) for acoustic impedance inversion. The workflow contains three networks: a generator, a discriminator and a forward model. The training of the generator and discriminator are guided by well logs and constrained by unlabeled data via the forward model. The benchmark models Marmousi2, SEAM and a field data are used to demonstrate the performance of our method. Results show that impedance predicted by the presented method, due to making use of both labeled and unlabeled data, are better consistent with ground truth than that of conventional deep learning methods