Introduction: The prognosis of advanced hepatocellular carcinoma (HCC) varies in patients receiving transcatheter arterial chemoembolization (TACE). In this study, we aimed to assess the prognostic ...value of serum apolipoprotein B (ApoB)/apolipoprotein A-I (ApoA-I) in this group of patients. Methods: The serum lipid levels of HCC patients undergoing TACE were obtained from routine preoperative blood lipid examination. A propensity score-matched (PSM) analysis was used to eliminate the imbalance of baseline characteristics of the high and low ApoB/ApoA-I groups. Then, univariate and multivariate analysis were conducted to evaluate the prognostic value of ApoB/ApoA-I. Results: In 455 HCC patients treated with TACE, ApoB/ApoA-I was positively correlated with AFP, T stage, distant metastasis, and TNM stage (p < 0.05). Patients with high ApoB/ApoA-I had a significantly shorter overall survival (OS) than those with low ApoB/ApoA-I (median OS, 21.7 vs. 39.6 months, p < 0.001). Multivariate analysis indicated that ApoB/ApoA-I was an independent prognostic index for OS (hazard ratio HR = 1.42, p = 0.008). After baseline characteristics were balanced, 288 patients were included in the PSM cohort. In this cohort, high ApoB/ApoA-I still predicted inferior OS in both univariate analysis (median OS, 27.6 vs. 39.3 months, p = 0.002) and multivariate analysis (HR = 1.58, p = 0.006). Conclusion: Serum ApoB/ApoA-I is a useful biomarker in predicting aggressive clinicopathological characteristics and poor prognosis in HCC patients treated with TACE.
High-dimensional (HD) entanglement provides a very promising way of transcending the limitations of the two-dimensional entanglement between qubits for increasing channel capacity in many quantum ...protocols. In the pursuit of capitalizing on the HD entangled states, one of the central issues is to unambiguously and comprehensively quantify and reconstruct them. The full quantum state tomography is a unique solution, but it is undesirable and even impractical because the measurements increase rapidly in
d
4
for a bipartite
d
-dimensional quantum state. Here we present a very efficient and practical tomography method—asymptotical locking tomography (ALT), which can harvest full information of bipartite
d
-dimensional entangled states by very few measurements less than 2
d
2
only. To showcase the validity and reasonableness of our ALT, we carry out the test with the two-photon spin-orbital angular momentum hyperentangled states in a four-dimensional subspace. Besides high-efficiency and practicality, our ALT is also universal and can be generalized into multipartite HD entanglement and other quantum systems.
To characterize human leukocyte antigen (HLA) loci as risk factors in aromatic antiepileptic drug-induced maculopapular exanthema (AED-MPE). A case-control study was performed to investigate HLA loci ...involved in AED-MPE in a southern Han Chinese population. Between January 2007 and June 2019, 267 patients with carbamazepine (CBZ), oxcarbazepine (OXC), or lamotrigine (LTG) associated MPE and 387 matched drug-tolerant controls from six centers were enrolled. HLA-A/B/C/DRB1 genotypes were determined using sequence-based typing. Potential risk alleles were validated by meta-analysis using data from different populations and
in silico
analysis of protein-drug interactions. HLA-DRB1*04:06 was significantly associated with OXC-MPE (
p
= 0.002,
p
c
= 0.04). HLA-B*38:02 was associated with CBZ-MPE (
p =
0.03). When pooled, HLA-A*24:02, HLA-A*30:01, and HLA-B*35:01 additionally revealed significant association with AED-MPE. Logistic regression analysis showed a multiplicative interaction between HLA-A*24:02 and HLA-B*38:02 in CBZ-MPE. Meta-analysis of data from different populations revealed that HLA-24*:02 and HLA-A*30:01 were associated with AED-MPE (
p
= 0.02 and
p
= 0.04, respectively).
In silico
analysis of protein-drug interaction demonstrated that HLA-A*24:02 and HLA-A*30:01 had higher affinities with the three aromatic AEDs than the risk-free HLA-A allele. HLA-DRB1*04:06 showed relatively specific high affinity with S-monohydroxy derivative of OXC. HLA-DRB1*04:06 is a specific risk allele for OXC-induced MPE in the Southern Han Chinese. HLA-A*24:02, possibly HLA-A*30:01, are common risk factors for AED-MPE. The multiplicative risk potential between HLA-A*24:02 and HLA-B*38:02 suggests that patients with two risk alleles are at greater risk than those with one risk allele. Inclusion of these HLA alleles in pre-treatment screening would help estimating the risk of AED-MPE.
The promising benefits of salidroside (SAL) in alleviating high altitude sickness boost investigations on its pharmacokinetics and biological activity. However, the transportation and disposition ...process of SAL under hypoxic conditions has never been explored. The current study was proposed to investigate the pharmacokinetics of SAL in hypoxic rats and to explore the underlying mechanisms for the distinct metabolic fate of SAL under hypoxia. Pharmacokinetic studies on SAL was conducted in both hypoxic and normoxic rats. The transport properties of SAL were investigated on both hypoxic and normoxic Caco-2 monolayer models. Enzymes involved in SAL metabolism were identified and the effects of hypoxia on these enzymes were assessed by real-time PCR, western blotting analyses, and rat liver homogenate incubation. The renal clearance (CL
r
) of SAL, effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) in both hypoxic and normoxic rats were also determined for renal function assessment. It was found that the systemic exposure of SAL in hypoxic rats was remarkably higher than that in normoxic rats. The barrier function of Caco-2 monolayer was weakened under hypoxia due to the impaired brush border microvilli and decreased expression of tight junction protein. Hepatic metabolism of SAL in hypoxic rats was attenuated due to the reduced activity of cytosolic β-glucosidase (CBG). Moreover, CL
r
of SAL was reduced in hypoxic rats due to the suppressed ERPF. Our findings suggest the potential need for dose-adjustment of SAL or its structural analogs under hypoxic conditions.
CBG inhibition and renal blood flow suppression are leading causes for the enhanced systemic exposure of SAL in hypoxic rats.
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IJS, KILJ, NUK, UL, UM, UPUK
The accurate hydrodynamic description of an event or system that addresses the equations of state, phase transitions, dissociations, ionizations, and compressions, determines how materials respond to ...a wide range of physical environments. To understand dense matter behavior in extreme conditions requires the continual development of diagnostic methods for accurate measurements of the physical parameters. Here, we present a comprehensive diagnostic technique that comprises optical pyrometry, velocity interferometry, and time-resolved spectroscopy. This technique was applied to shock compression experiments of dense gaseous deuterium–helium mixtures driven via a two-stage light gas gun. The advantage of this approach lies in providing measurements of multiple physical parameters in a single experiment, such as light radiation histories, particle velocity profiles, and time-resolved spectra, which enables simultaneous measurements of shock velocity, particle velocity, pressure, density, and temperature and expands understanding of dense high pressure shock situations. The combination of multiple diagnostics also allows different experimental observables to be measured and cross-checked. Additionally, it implements an accurate measurement of the principal Hugoniots of deuterium−helium mixtures, which provides a benchmark for the impedance matching measurement technique.
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•Cu-based metal covalent organic framework (Cu-TMT) was prepared for the extraction of uranium.•Cu-TMT has unsaturated Cu centers that serve as chemical reduction sites.•Cu-TMT has ...excellent visible light conversion efficiency and low band gap.•Cu-TMT reduced uranium by chemical reduction and photocatalytic reduction reached 1438.8 mg g−1.
The reduction of hexavalent uranium to tetravalent uranium is an effective strategy for controlling uranium contamination in wastewater. Herein, a CC bonded metal-covalent organic framework (Cu-TMT) was synthesized via the Aldol condensation reaction by using the metal cluster Cu3(PyCA)3 and 2,4,6-trimethyl-1,3,5-triazine (TMT) for the chemical and photocatalytic synergistic reduction of uranium. In the Cu-TMT, the low-valent Cu in the metal clusters provides the framework with numerous distributed redox sites being capable of chemically reducing UVI. Meanwhile, the encapsulating Cu clusters in long-range ordered frameworks can provide fast transport channels for intramolecular charge transfer and effectively inhibit electron/hole complexation, making Cu-TMT suitable for photocatalytic reduction of uranium. The chemical reduction of uranium by Cu-TMT was verified under light-avoidance conditions, reaching 659.5 mg g−1. After exposure of Cu-TMT to light, the amount of reduced uranium further increases to 1438.8 mg g−1 with 98.1 % removal rate of actual uranium containing wastewater. This study not only expands the range of applications of variable valence metal covalent organic frameworks, but also provides unique insights into the effective combination of chemical and photocatalytic reduction strategies for removing UVI in a single material.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This ...phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6-18.0) for the immunotherapy group compared with 9.9 months (8.0-11.8) for the control group (hazard ratio HR, 0.60 95% CI, 0.40-0.88; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3-32.8) for the control group (HR, 0.57 95% CI, 0.33-0.98; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.
Micromachined gyroscopes require high voltage (HV) for actuation and detection to improve its precision, but the deviation of the HV caused by temperature fluctuations will degrade the sensor’s ...performance. In this paper, a high-voltage temperature-insensitive charge pump is proposed. Without adopting BCD (bipolar-CMOS-DMOS) technology, the output voltage can be boosted over the breakdown voltage of n-well/substrate diode using triple-well NMOS (n-type metal-oxide-semiconductor) transistors. By controlling the pumping clock’s amplitude continuously, closed-loop regulation is realized to reduce the output voltage’s sensitivity to temperature changes. Besides, the output level is programmable linearly in a large range by changing the reference voltage. The whole circuit has been fabricated in a 0.18- μ m standard CMOS (complementary metal-oxide-semiconductor) process with a total area of 2.53 mm 2 . Measurements indicate that its output voltage has a linear adjustable range from around 13 V to 16.95 V, and temperature tests show that the maximum variations of the output voltage at − 40 ∼ 80 ∘ C are less than 1.1%.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Whether Li-S batteries can be worked in a wider temperature range is particularly important. Here, we report micro/nanostructure CoFe
2
O
4
rods combining both catalytic sites (Co) and adsorption ...sites (Fe). Under the synergistic enhancement of these two different sites, the conversion rate of polysulfides in Li-S batteries is greatly accelerated, and the "shuttle effect" is effectively suppressed. When used as the host material for Li-S batteries, the capacity, rate performance and cycling stability are promoted greatly. Most importantly, the cell achieves an excellent electrochemical performance at high temperatures. After 1000 cycles, the Li-S battery using CoFe
2
O
4
nanorods as the cathode exhibits a high reversible capacity of about 700 mA h g
−1
at a high temperature of 70 °C with a capacity attenuation of less than 0.02% per cycle. Meanwhile, the battery also shows excellent performance at −20 °C owing to the high catalytic activity.
Due to the synergistic strengthening of the Co catalytic center and Fe adsorption center in the CoFe
2
O
4
nanorods which used as a host material for a Li-S battery. The effective working temperature of the battery is widened to −20 to 70 °C.
Carcinosarcoma of the liver is very rare worldwide. The terminology and pathogenesis of hepatic carcinosarcoma remain controversial issues. In this article, we studied the clinicopathologic features ...of 5 cases of hepatic carcinosarcomas (matching the World Health Organization definition), analyzed the clinical data, histologic and immunohistochemical (IHC) results, and discussed the terminology, pathologic differential diagnoses, pathogenesis, and prognosis. The patients were 40 to 68 years old, and included 4 males and 1 female. All patients were Hepatitis B surface antigen positive with para-tumorous cirrhosis. The largest dimensions of the neoplasms ranged from 6.0 to 14.0 cm. Satellite nodules, portal vein tumor thrombi, direct invasion into local tissues (right diaphragm, right adrenal gland, and gastric wall) as well as metastatic foci in lungs and abdominal lymph nodes were identified. Pathologically, the neoplasms consisted of carcinomatous and sarcomatous components. The carcinomatous components were exclusively conventional hepatocellular carcinomas in all 5 cases, whereas the sarcomatous components exhibited complex features. Confirmed by IHC studies, the sarcomatous elements in different cases included rhabdomyosarcomas, malignant fibrous histiocytomas, fibrosarcoma, and poorly differentiated spindle cells without distinctive differentiation. Furthermore, the sarcomatous elements in these 5 neoplasms stained negative for all the epithelial markers we applied for IHC staining, which support the pathologic diagnosis of carcinosarcoma rather than sarcomatoid carcinoma. The presence of transitional zones between carcinomatous and sarcomatous components may support the transformation theory. Four patients with palliative hepatectomy died within 6 months, whereas 1 patient is still alive 21 months after radical resection. The poor prognosis of hepatic carcinosarcoma may be due to their highly invasive and metastatic features. Radical resection of early stage hepatic carcinosarcoma may contribute to a relatively optimistic prognosis.
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