Essentials
Perioperative blood loss and inflammatory response can significantly affect recovery after surgery.
We studied the effects of multiple‐dose oral tranexamic acid on blood loss and ...inflammatory response.
A postoperative four‐dose regimen brought about maximum reduction in postoperative blood loss.
A postoperative four‐dose regimen reduced inflammatory response and promoted early rehabilitation.
Summary
Background
Tranexamic acid (TXA) can reduce blood loss and the inflammatory response at multiple doses in total knee arthroplasty patients. However, the optimal regimen has not been determined.
Objectives
To identify the most effective regimen for achieving maximum reductions in blood loss and the inflammatory response.
Patients/Methods
Two hundred and seventy‐five patients were randomized to receive a placebo (group A), a single 2‐g oral dose of TXA 2 h preoperatively followed by 1 g of oral TXA 3 h postoperatively (group B), a single dose followed by 1 g of oral TXA 3 h and 7 h postoperatively (group C), a single dose followed by 1 g of oral TXA 3 h, 7 h and 11 h postoperatively (group D), or a single dose followed by 1 g of oral TXA 3 h, 7 h, 11 h and 15 h postoperatively (group E). The primary outcome was total blood loss on postoperative day (POD) 3. Secondary outcomes included a decrease in the hemoglobin level, coagulation parameters, inflammatory marker levels, and thromboembolic complications.
Results
Groups D and E had significantly lower blood loss and smaller decreases in hemoglobin level than groups A, B, and C, with no significant difference on POD 3 between groups D and E. Significantly enhanced coagulation was identified for the four multiple‐dose regimens; however, all thromboelastographic parameters remained within normal ranges. Group E had the lowest inflammatory marker levels and pain, and the greatest range of motion. No thromboembolic complications were identified.
Conclusion
The four‐dose regimen yielded the maximum reductions in blood loss and inflammatory response, improved analgesia, and promoted early rehabilitation. Further studies are required to ensure that these findings are reproducible.
Subclinical hypothyroidism (SCH) has been shown to be associated with microbiota. However, the association between SCH and oral microbiota has not yet been elucidated. The results of our previous ...clinical studies showed that Prevotella intermedia was abundant in the oral microbiota of SCH patients. This study aimed to investigate the relationship between SCH and oral microbiota, verify the pathogenicity of P. intermedia in SCH, and preliminarily explore the possible mechanism. The SCH mouse model with oral application of P. intermedia was established, and the variance in the mouse oral microbiota and changes in thyroid function and metabolism were detected in mice. Student’s t test and analysis of variance were used for statistical analysis. Oral application of P. intermedia changed the composition of the oral microbiota of SCH mice, which enhanced the damage to the thyroid and decreased the expression of functional genes of the thyroid. Moreover, P. intermedia decreased oxygen consumption and aggravated glucose and lipid metabolism disorders in SCH mice. Glucose tolerance and insulin tolerance decreased, and the triglyceride content of the liver and inflammatory infiltration in adipose tissue increased in SCH mice after P. intermedia stimulation. Mechanistically, P. intermedia increased the proportion of CD4+ T cells in cervical lymph nodes and thyroids in SCH mice. Th1 cells were suggested to play an important role in the pathogenesis of SCH involving P. intermedia. In conclusion, P. intermedia aggravated SCH manifestations, including thyroid dysfunction and glucose and lipid metabolism disorders, by causing immune imbalance in mice. This study sheds new light on the pathogenesis of SCH from the perspective of oral microbiota.
AlxCrFeNi eutectic multi-component alloys were prepared to obtain excellent mechanical properties by double-phase strengthening. The X-ray diffraction results showed that the crystal structure were ...both body-centered cubic and energy-dispersive X-ray spectrometer identified that the two phases are ordered NiAl intermetallic and disordered Fe, Cr solid solution. The formation of eutectic structures was introduced by a simplified dynamic model. After mechanical tests, the alloys presented excellent compressive strength and unexpected large deformation. Due to the solid solution and fine-grain strengthening resulted by Al addition, mechanical properties of AlxCrFeNi alloys exhibited regularity in some degree. Among all alloys, Al1.3CrFeNi has the highest fracture strength and Al0.9CrFeNi has the most excellent strain. Besides, Al1.2CrFeNi alloy showed a good combination of strength and ductility.
At sufficiently low temperatures, condensed-matter systems tend to develop order. A notable exception to this behaviour is the case of quantum spin liquids, in which quantum fluctuations prevent a ...transition to an ordered state down to the lowest temperatures. There have now been tentative observations of such states in some two-dimensional organic compounds, yet quantum spin liquids remain elusive in microscopic two-dimensional models that are relevant to experiments. Here we show, by means of large-scale quantum Monte Carlo simulations of correlated fermions on a honeycomb lattice (a structure realized in, for example, graphene), that a quantum spin liquid emerges between the state described by massless Dirac fermions and an antiferromagnetically ordered Mott insulator. This unexpected quantum-disordered state is found to be a short-range resonating valence-bond liquid, akin to the one proposed for high-temperature superconductors: the possibility of unconventional superconductivity through doping therefore arises in our system. We foresee the experimental realization of this model system using ultra-cold atoms, or group IV elements arranged in honeycomb lattices.
Physical activity has been shown to suppress tumor initiation and progression. The neurotransmitter dopamine (DA) is closely related to movement and exhibits antitumor properties. However, whether ...the suppressive effects of physical activity on tumors was mediated by the nervous system via increased DA level remains unknowns. Here we show that regular moderate swimming (8 min/day, 9 weeks) raised DA levels in the prefrontal cortex, serum and tumor tissue, suppressed growth, reduced lung metastasis of transplanted liver cancer, and prolonged survival in a C57BL/6 mouse model, while overload swimming (16 and 32 min/day, 9 weeks) had the opposite effect. In nude mice that were orthotopically implanted with human liver cancer cell lines, DA treatment significantly suppressed growth and lung metastasis by acting on the D2 receptor (DR2). Furthermore, DR2 blockade attenuated the suppressive effect of moderate swimming on liver cancer. Both moderate swimming and DA treatment suppressed the transforming growth factor-beta (TGF-β1)-induced epithelial-mesenchymal transition of transplanted liver cancer cells. At the molecular level, DR2 signaling inhibited extracellular signal-regulated kinase phosphorylation and expression of TGF-β1 in vitro. Together, these findings demonstrated a novel mechanism by which the moderate exercise suppressed liver cancer through boosting DR2 activity, while overload exercise had the opposite effect, highlighting the possible importance of the dopaminergic system in tumor growth and metastasis of liver cancer.
ABSTRACT
We report the phase-connected timing ephemeris, polarization pulse profiles, Faraday rotation measurements, and Rotating-Vector-Model (RVM) fitting results of 12 millisecond pulsars (MSPs) ...discovered with the Five-hundred-meter Aperture Spherical radio Telescope (FAST) in the Commensal Radio Astronomy FAST survey (CRAFTS). The timing campaigns were carried out with FAST and Arecibo over 3 yr. 11 of the 12 pulsars are in neutron star–white dwarf binary systems, with orbital periods between 2.4 and 100 d. 10 of them have spin periods, companion masses, and orbital eccentricities that are consistent with the theoretical expectations for MSP–Helium white dwarf (He WD) systems. The last binary pulsar (PSR J1912−0952) has a significantly smaller spin frequency and a smaller companion mass, the latter could be caused by a low orbital inclination for the system. Its orbital period of 29 d is well within the range of orbital periods where some MSP–He WD systems have shown anomalous eccentricities, however, the eccentricity of PSR J1912−0952 is typical of what one finds for the remaining MSP–He WD systems.
Epidermal growth factor receptor (EGFR) regulates multiple signaling cascades essential for cell proliferation, growth and differentiation. Using a genetic approach, we found that Drosophila FERM and ...PDZ domain-containing protein tyrosine phosphatase, dPtpmeg, negatively regulates border cell migration and inhibits the EGFR/Ras/mitogen-activated protein kinase signaling pathway during wing morphogenesis. We further identified EGFR pathway substrate 15 (Eps15) as a target of dPtpmeg and its human homolog PTPN3. Eps15 is a scaffolding adaptor protein known to be involved in EGFR endocytosis and trafficking. Interestingly, PTPN3-mediated tyrosine dephosphorylation of Eps15 promotes EGFR for lipid raft-mediated endocytosis and lysosomal degradation. PTPN3 and the Eps15 tyrosine phosphorylation-deficient mutant suppress non-small-cell lung cancer cell growth and migration in vitro and reduce lung tumor xenograft growth in vivo. Moreover, depletion of PTPN3 impairs the degradation of EGFR and enhances proliferation and tumorigenicity of lung cancer cells. Taken together, these results indicate that PTPN3 may act as a tumor suppressor in lung cancer through its modulation of EGFR signaling.
Abstract We report the timing analysis of PSR J1846−0513, a pulsar discovered by the Five-hundred-meter Aperture Spherical radio Telescope (FAST) in Commensal Radio Astronomy FAST Survey. The pulsar ...possesses a spin period of 23.36 ms and a spin-down rate ( P ̇ ) of 1.0106(3) × 10 −18 s s −1 , and it is located in an eccentric orbit ( e ∼0.208) with an orbital period of 0.61 days. The characteristic age and surface magnetic field of the pulsar are found to be 366.62 Myr and 4.9178 × 10 9 G, respectively, indicating that it is a recycled pulsar. Using over two years of timing data, we measure the periastron advance ω ̇ = 0.8956(8) deg yr −1 . By assuming that this effect is purely relativistic, we have estimated the total mass M = 2.6287(35) M ⊙ and obtained an upper limit for the pulsar mass and a lower limit for the companion’s mass. Our results indicate that this is a double neutron star system.
Electrically assisted (EA) forming has ubiquitous merits over room-temperature (RT) forming and thermally aided forming for the fabrication of difficult-to-form microscale products. However, it is ...difficult to predict the material deformation behavior in the EA microforming process owing to the coupling between the electric current and microstructural size effect. To develop a robust constitutive model that considers the interplay between the electric and grain size effects, RT and EA quasi-static uniaxial tensile tests were performed on ultrathin nickel-based superalloy sheets with a thickness of 0.2 mm and grain sizes ranging from 27.2 to 79.4 μm. The experimental results demonstrated that the Joule heating effect and the normalized flow stress reduction were non-monotonically related to the grain size of the superalloy. The grain size effect in the polycrystalline superalloy was suppressed by the enhanced current density. A multiscale constitutive model that considered multiple strengthening mechanisms was proposed to describe the EA deformation behavior of ultrathin superalloy sheets. The multiscale model was proven to have a desirable predictive ability for the EA drawing force of thin-walled superalloy capillaries. Furthermore, the model revealed that the weakening of the grain size effect with increasing current density in the polycrystalline superalloy was caused by the combined variations in dislocation interaction, shear modulus, and strengthening mechanisms. The abnormal evolution of the surface effect with the current density was captured by the proposed constitutive model, which demonstrates that the electric current can promote the grain size effect in the multicrystalline superalloy.
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•Grain size effect in electrically assisted deformation of ultrathin superalloy sheets was investigated.•Dislocation density model was modified and verified to consider grain size and electroplastic effects.•Joule heating effect and normalized flow stress reduction are non-monotonically related to grain size.•Pulsed current suppresses the grain size effect of polycrystalline, but promotes that for multicrystalline.
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