A novel GATA1 variant p.G229D causing the defect of procoagulant platelet formation.

INTRODUCTION: GATA1 is one of the master transcription factors in hematopoietic lineages development which is crucial for megakaryocytic differentiation and maturation. Previous studies have shown that distinct GATA1 variants are associated with varying severities of macrothrombocytopenia and platelet dysfunction. OBJECTIVE: To determine the underlying pathological mechanisms of a novel GATA1 variant (c. 686G > A, p. G229D) in a patient with recurrent traumatic muscle hematomas. METHODS: Comprehensive phenotypic analysis of the patient platelets was performed. Procoagulant platelet formation and function were detected using flow cytometry assay and thrombin generation test (TGT), respectively. The ANO6 expression was measured by qPCR and western blot. The intracellular supramaximal calcium flux was detected by Fluo-5N fluorescent assay. RESULTS: The patient displayed mild macrothrombocytopenia with defects of platelet granules, aggregation, and integrin αIIbß3 activation. The percentage of the procoagulant platelet formation of the patient upon the stimulation of thrombin plus collagen was lower than that of the healthy controls (40.9 % vs 49.0 % ± 5.1 %). The patient platelets exhibited a marked reduction of thrombin generation in platelet rich plasma TGT compared to the healthy controls (peak value: ∼70 % of the healthy controls; the endogenous thrombin potential: ∼40 % of the healthy controls). The expression of ANO6 and intracellular calcium flux were impaired, which together with abnormal granules of the patient platelets might contribute to defect of procoagulant platelet function. CONCLUSIONS: The G229D variant could lead to a novel platelet phenotype characterized by defective procoagulant platelet formation and function, which extended the range of GATA1 variants associated platelet disorders.

Structural and functional exploration of three newly identified coagulation factor IX mutations in Chinese hemophilia B patients.

AIM: To structurally and functionally characterize three newly identified F9 missense mutations, C268Y, I316F, and G413V, in Chinese hemophilia B patients. METHODS: FIX mutants were expressed in vitro by transient transfection of Chinese hamster ovary (CHO) cells. One-stage activated partial thromboplastin time (APTT) based assay and enzyme-linked immunosorbent assay (ELISA) were used to measure the coagulation activity and antigen level of FIX in conditioned medium. Western blot analysis was also used to evaluate interference of the mutations with synthesis and secretion of FIX. A structural model of the FIX G413V mutant was constructed and structural disturbance caused by the mutation was determined by molecular dynamics simulations. RESULTS: Both C268Y and I316F impaired expression of FIX. However, the I316F mutant degraded quickly, whereas the C268Y mutant mostly accumulated intracellularly. The G413V mutant could be synthesized and secreted normally, but procoagulant activity was almost completely lost. This loss is likely mostly due to the impact on the catalytic residue cS195. CONCLUSION: The three FIX mutations identified in Chinese hemophilia B patients either impaired the expression of FIX, as was seen with the I316F and C268Y mutants, or impaired the function of FIX, as was seen with the G413V mutant.

Extraskeletal mesenchymal chondrosarcoma of the distal thumb: A case report.

INTRODUCTION AND IMPORTANCE: Chondrosarcoma is the most common primary malignant bone tumor of the hand, Mesenchymal chondrosarcoma (MCS) is a rare subtype of chondrosarcoma, extraosseous mesenchymal chondrosarcoma (EMCS) is even rarer. CASE PRESENTATION: We presented a case of primary EMCS involving the distal thumb in a 59-year-old man. The patient had abnormally grown nails and a higher skin temperature than the contralateral finger. After admission to our hospital, we found that the tumor has the possibility of malignant transformation, but imageological examinations did not reveal invasive bone lesions and calcification. Finally, due to the patient's strong desire to preserve the thumb, a conservative surgical approach was selected to preserve the patient's finger function, and histological examination indicated MCS. CONCLUSION: EMCS is a highly malignant tumor with strong tendency of invasion and metastasis. Imaging is sometimes difficult to diagnose, and pathology is a necessary part of distinguishing between benign and malignant tumors. Operation is the major treatment to EMCS, meanwhile, adjuvant radiotherapy and chemotherapy also be effective. The overall prognosis is poor.

Comparison of the clinical efficacy of percutaneous transforaminal endoscopic discectomy and traditional laminectomy in the treatment of recurrent lumbar disc herniation.

ABSTRACT: A few years ago, percutaneous transforaminal endoscopic discectomy (PTED) began to prevail in clinical treatment of recurrent lumbar disc herniation (RLDH), whereas traditional laminectomy (TL) was treated earlier in RLDH than PTED. This study aimed to compare the clinical efficacy of PTED and TL in the treatment of RLDH.Between November 2012 and October 2017, retrospective analysis of 48 patients with RLDH who were treated at the Cancer Hospital, Chinese Academy of Sciences, Hefei and Department of Orthopaedics, Second Affiliated Hospital of Anhui Medical University. Perioperative evaluation indicators included operation time, the intraoperative blood loss, length of incision and hospitalization time. Clinical outcomes were measured preoperatively, and at 1 days, 3 months, and 12 months postoperatively. The patients' lower limb pain was evaluated using Oswestry disability index (ODI) and visual analog scale (VAS) scores. The ODI is the most widely-used assessment method internationally for lumbar or leg pain at present. Every category comprises 6 options, with the highest score for each question being 5 points. higher scores represent more serious dysfunction. The VAS is the most commonly-used quantitative method for assessing the degree of pain in clinical practice. The measurement method is to draw a 10 cm horizontal line on a piece of paper, 1 end of which is 0, indicating no pain, which the other end is 10, which means severe pain, and the middle part indicates different degree of pain.Compared with the TL group, the operation time, postoperative bed-rest time, and hospitalization time of the PTED group were significantly shorter, and the intraoperative blood loss was also reduced. These differences were statistically significant (P < .01). There were no significant differences in VAS or ODI scores between the two groups before or after surgery (P > .05).PTED and TL have similar clinical efficacy in the treatment of RLDH, but PTED can shorten the operation time, postoperative bed-rest time and hospitalization time, and reduce intraoperative blood loss, so the PTED is a safe and effective surgical method for the treatment of RLDH than TL, but more randomized controlled trials are still required to further verify these conclusions.

MicroRNA-495 inhibits the high glucose-induced inflammation, differentiation and extracellular matrix accumulation of cardiac fibroblasts through downregulation of NOD1.

BACKGROUND: MicroRNAs (miRNAs) have physiological and pathophysiological functions that are involved in the regulation of cardiac fibrosis. This study aimed to investigate the effects of miR-495 on high glucose-induced cardiac fibrosis in human cardiac fibroblasts (CFs) and to establish the mechanism underlying these effects. METHODS: Human CFs were transfected with an miR-495 inhibitor or mimic and incubated with high glucose. The levels of NOD1 and miR-495 were then determined via quantitative RT-PCR. Pro-inflammatory cytokine levels, cell differentiation and extracellular matrix accumulation were respectively detected using ELISA, quantitative RT-PCR and western blot assays. The luciferase reporter assay, quantitative RT-PCR and western blot were used to explore whether NOD1 was a target of miR-495. The effects of miR-495 on the NF-κB and TGF-ß1/Smad signaling pathways were also detected via western blot. RESULTS: Our results show that high glucose can significantly increase the expression of NOD1 in a time-dependent manner. Upregulation of miR-495 significantly alleviated the high glucose-induced increases in cell differentiation and collagen accumulation of CFs. Moreover, the bioinformatics analysis predicted that NOD1 was a potential target gene for miR-495. The luciferase reporter assay showed that miR-495 can directly target NOD1. The introduction of miR-495 could significantly inhibit the high glucose-activated NF-κB and TGF-ß1/Smad signaling pathways. CONCLUSION: Upregulation of miR-495 ameliorates the high glucose-induced inflammatory, cell differentiation and extracellular matrix accumulation of human CFs by modulating both the NF-κB and TGF-ß1/Smad signaling pathways through downregulation of NOD1 expression. These results provide further evidence for the protective effect of miR-495 overexpression in cases of high glucose-induced cardiac fibrosis.

Echocardiography and Electrocardiography Variables Correlate With the New York Heart Association classification: An Observational Study of Ischemic Cardiomyopathy Patients.

The aim of our study was to determine whether combinations of ultrasound echocardiography (UCG) and electrocardiography (EKG) parameters correlated with the functional status of ischemic cardiomyopathy (ICM) patients according to the New York Heart Association (NYHA) classification system.We assessed 536 elderly Chinese ICM patients according to the NYHA criteria, which included 196 patients with type 2 diabetes mellitus (T2DM). All of the patients underwent UCG. Transmural dispersion of ventricular repolarization was examined using EKG. Cumulative odds logistic regression was performed to evaluate associations between NYHA class and the demographic, clinical, UCG, and EKG variables based on the odds ratio (OR) and 95% confidence interval (CI). A Pearson analysis was also performed to examine correlations between the NYHA classification and the UCG and EKG variables.Based on the NYHA assessment, 140, 147, 138, and 111 patients were identified as class I, II, III and IV, respectively. A comparison of UCG and EKG variables based on T2DM status showed that CO and Tp-e differed significantly between all NYHA classes (P < .05 for all), with values of each increasing with increasing NYHA class regardless of T2DM status. Multivariate logistic regression analysis showed that the disease course (OR: 1.30; 95% CI: 1.20-1.40), heart rate (OR: 1.16; 95% CI: 1.12-1.21), T wave peak to endpoint (Tp-e; OR: 1.22; 95% CI: 1.18-1.27), dispersion of the QT interval (OR: 0.98; 95% CI: 0.95-1.22), left ventricular fractional shortening (OR: 0.82; 95% CI: 0.78-0.87), cardiac output (CO; OR: 5.58; 95% CI: 3.08-10.13) were significantly associated with the NYHA class (P < .0001 for all). A Pearson correlation analysis showed that Tp-e (r = 0.75982, P < .0001), CO (r = 0.56072, P < .0001), and stroke volume (r = -0.14839, P = .0006) significantly correlated with the NYHA class.An index consisting of Tp-e and CO will be useful for corroborating the results of the NYHA assessment of ICM patients.

Impact of self-phase modulation on coherently combined fiber chirped-pulse amplifiers.

The impact of self-phase modulation on coherently combined ultrafast fiber-based chirped-pulse amplifiers (CPA) is studied. We point out that, in nonlinear CPA regime, the nonlinear phase accumulated in each fiber amplifier can significantly differ from one to another, resulting in serious efficiency degradation of coherent combining. A test bench based on picosecond pulses, and a single fiber amplifier is developed to experimentally demonstrate the effect. The effects that can lead to this nonlinear phase deviation and the induced system limitations are discussed and analyzed.

Self-referenced and single-ended method to measure Brillouin gain in monomode optical fibers.

We present a new self-referenced and single-ended method to measure the Brillouin-gain coefficient in monomode optical fibers accurately with high reliability. Our comparative measurements on several different fibers show that a fiber with a smaller optical effective mode area can nevertheless have a higher Brillouin threshold, thus confirming the significance of acousto-optic effective mode area.

Full characterization of modern transmission fibers for Raman amplified-based communication systems.

Telecommunication carriers have to estimate the Raman parameters of the fibers installed on their optical transport networks in order to facilitate the design of the next generation of high bit-rate Raman amplified-based transmission systems. This paper reports a very complete characterization of the most popular modern transmission fibers in terms of Raman efficiency, noise figure and double Rayleigh backscattering crosstalk. Our experiment is based on an averaged power analysis, applied to a counter-pumped long-haul distributed fiber Raman amplifier. We evaluate as well at 40 Gb/s for these different fiber types the double Rayleigh backscattering impact in terms of Q-factor penalty for various Raman gains and RZ modulation formats with different duty cycles.