Postoperative morbidity after curative resection for hilar cholangiocarcinoma (HCCA) is common; however, whether it has an impact on oncological prognosis is unknown.
To evaluate the influence of ...postoperative morbidity on tumor recurrence and mortality after curative resection for HCCA.
Patients with recently diagnosed HCCA who had undergone curative resection between January 2010 and December 2017 at The First Affiliated Hospital of Army Medical University in China were enrolled. The independent risk factors for morbidity in the 30 d after surgery were investigated, and links between postoperative morbidity and patient characteristics and outcomes were assessed. Postoperative morbidities were divided into five grades based on the Clavien-Dindo classification, and major morbidities were defined as Clavien-Dindo ≥ 3. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for recurrence-free survival (RFS) and overall survival (OS).
Postoperative morbidity occurred in 146 out of 239 patients (61.1%). Multivariate logistic regression revealed that cirrhosis, intraoperative blood loss > 500 mL, diabetes mellitus, and obesity were independent risk factors. Postoperative morbidity was associated with decreased OS and RFS (OS: 18.0 mo
31.0 mo, respectively,
= 0.003; RFS: 16.0 mo
26.0 mo, respectively,
= 0.002). Multivariate Cox regression analysis indicated that postoperative morbidity was independently associated with decreased OS hazard ratios (HR): 1.557, 95% confidence interval (CI): 1.119-2.167,
= 0.009 and RFS (HR: 1.535, 95%CI: 1.117-2.108,
= 0.008). Moreover, major morbidity was independently associated with decreased OS (HR: 2.175; 95%CI: 1.470-3.216,
< 0.001) and RFS (HR: 2.054; 95%CI: 1.400-3.014,
< 0.001) after curative resection for HCCA.
Postoperative morbidity (especially major morbidity) may be an independent risk factor for unfavorable prognosis in HCCA patients following curative resection.
•There is a synergistic effect between intranasal NGF and ventricle NSCs grafts.•Combined therapy can enhance motor function, delay the onset, and prolong survival.•Combined therapy can promote nerve ...regeneration and protect motor neurons.
Amyotrophic lateral sclerosis (ALS) is a fatal disease that selectively involves motor neurons. Neurotrophic factor supplementation and neural stem cell (NSC) alternative therapy have been used to treat ALS. The two approaches can affect each other in their pathways of action, and there is a possibility for synergism. However, to date, there have been no studies demonstrating the effects of combined therapy in the treatment of ALS. In this study, for the first time, we adopted a method involving the intranasal administration of nerve growth factor combined with lateral ventricle NSC transplantation using G93A-SOD1 transgenic mice as experimental subjects to explore the treatment effect of this combined therapy in ALS. We discover that the combined therapy increase the quantity of TrkA receptors, broaden the migration of exogenous NSCs, further promote active proliferation in neurogenic regions of the brain and enhance the preservation of motor neurons in the spinal cord. Regarding physical activity, the combined therapy improved motor functions, further postponed ALS onset and extended the survival time of the mice.
Zebrafish and human genomes are highly homologous; however, despite this genomic similarity, adult zebrafish can achieve neuronal proliferation, regeneration and functional restoration within 6-8 ...weeks after spinal cord injury, whereas humans cannot. To analyze differentially expressed zebrafish genes between axon-regenerated neurons and axon-non-regenerated neurons after spinal cord injury, and to explore the key genes and pathways of axonal regeneration after spinal cord injury, microarray GSE56842 was analyzed using the online tool, GEO2R, in the Gene Expression Omnibus database. Gene ontology and protein-protein interaction networks were used to analyze the identified differentially expressed genes. Finally, we screened for genes and pathways that may play a role in spinal cord injury repair in zebrafish and mammals. A total of 636 differentially expressed genes were obtained, including 255 up-regulated and 381 down-regulated differentially expressed genes in axon-regenerated neurons. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were also obtained. A protein-protein interaction network contained 480 node genes and 1976 node connections. We also obtained the 10 hub genes with the highest correlation and the two modules with the highest score. The results showed that spectrin may promote axonal regeneration after spinal cord injury in zebrafish. Transforming growth factor beta signaling may inhibit repair after spinal cord injury in zebrafish. Focal adhesion or tight junctions may play an important role in the migration and proliferation of some cells, such as Schwann cells or neural progenitor cells, after spinal cord injury in zebrafish. Bioinformatic analysis identified key candidate genes and pathways in axonal regeneration after spinal cord injury in zebrafish, providing targets for treatment of spinal cord injury in mammals.
In this study, the effects of BaCu(B2O5) (BCB) additive on the low-temperature sintering behaviour, microstructure evolution and microwave dielectric properties of (Co0.35Zn0.65)TiNb2O8 (CZTN) ...ceramics were systematically investigated by introducing the additive into the solid-state sintering process. Adding BCB successfully lowered CZTN ceramics' sintering temp from 1150 °C to 925 °C while preserving their superior microwave dielectric properties at the lower temperature. However, excessive BCB tends to disrupt the equilibrium between the native ixiolite and rutile phases within the ceramic matrix, thereby instigating a relative augmentation of the rutile phase, ultimately culminating in a positive shift in the temperature coefficient of the resonant frequency. Specific experimental data show that the CZTN ceramics prepared with a BCB content of 4 wt% exhibited good microwave dielectric properties after sintering at 925 ℃ for 4 h: relative dielectric constant (εr) = 36.7, quality factor (Q × f) = 19,880 GHz, and τf = +14.2 ppm/℃. In addition, the ceramic system showed good chemical compatibility when co-fired with Ag without significant elemental diffusion. This work reveals the specific role of BCB in enhancing low-temperature sintering of CZTN ceramics and pinpoints its ideal addition range, thereby offering crucial scientific insights and technical support for developing high-performance microwave dielectric ceramics for LTCC technology.
The fundamental mechanisms of ultrafast demagnetization and magnetization recovery processes in ferromagnetic materials remain incompletely understood. The investigation of different dynamic features ...which depend on various physical quantities requires a more systematic approach. Here, the femtosecond laser-induced demagnetization and recovery dynamics in L10-Fe0.5Pt0.5 alloy film are studied by utilizing time-resolved magneto-optical Kerr measurements, focusing on their dependences of excitation fluence and ambient temperature over broad ranges. Ultrafast demagnetization dominated by Elliott-Yafet spin-flip scattering, and two-step magnetization recovery processes are found to be involved in all observations. The fast recovery time corresponding to spin–lattice relaxation is much shorter than that of many ferromagnets and increase with excitation fluence. These can be ascribed to the strong spin–orbit coupling (SOC) demonstrated in FePt and the reduction of transient magnetic anisotropy, respectively. Surprisingly, the demagnetization time exhibits no discernible correlation with ambient temperature. Two competitive factors are proposed to account for this phenomenon. On the other hand, the spin–lattice relaxation accelerates as temperature decreases due to enhanced SOC at lower ambient temperature. A semiquantitative analysis is given to get a visualized understanding. These results offer a comprehensive understanding of the dynamic characteristics of ultrafast demagnetization and recovery processes in iron-based materials with strong SOC, highlighting the potential for regulating the magnetization recovery process through temperature and laser fluence adjustments.
Apple（Malus×domestica） has been proposed as an important woody plant and the major cultivated fruit trees in temperate regions. Apple whole genome sequencing has been completed, which provided an ...excellent opportunity for genome-wide analysis of the synonymous codon usage patterns. In this study, a multivariate bioinformatics analysis was performed to reveal the characteristics of synonymous codon usage and the main factors affecting codon bias in apple. The neutrality, correspondence, and correlation analyses were performed by Codon W and SPSS（Statistical Product and Service Solutions） programs, indicating that the apple genome codon usage patterns were affected by mutational pressure and selective constraint. Meanwhile, coding sequence length and the hydrophobicity of proteins could also influence the codon usage patterns. In short, codon usage pattern analysis and determination of optimal codons has laid an important theoretical basis for genetic engineering, gene prediction and molecular evolution studies in apple.
We developed an H5/H7 trivalent inactivated vaccine by using Re-11, Re-12, and H7-Re2 vaccine seed viruses, which were generated by reverse genetics and derived their HA genes from ...A/duck/Guizhou/S4184/2017(H5N6) (DK/GZ/S4184/17) (a clade 2.3.4.4d virus), A/chicken/Liaoning/SD007/2017(H5N1) (CK/LN/SD007/17) (a clade 2.3.2.1d virus), and A/chicken/Guangxi/SD098/2017(H7N9) (CK/GX/SD098/17), respectively. The protective efficacy of this novel vaccine and that of the recently used H5/H7 bivalent inactivated vaccine against different H5 and H7N9 viruses was evaluated in chickens. We found that the H5/H7 bivalent vaccine provided solid protection against the H7N9 virus CK/GX/SD098/17, but only 50–60% protection against different H5 viruses. In contrast, the novel H5/H7 trivalent vaccine provided complete protection against the H5 and H7 viruses tested. Our study underscores the importance of timely updating of vaccines for avian influenza control.
Dysfunctional bone marrow (BM) endothelial progenitor cells (EPCs) with high levels of reactive oxygen species (ROS) are responsible for defective hematopoiesis in poor graft function (PGF) patients ...with acute leukemia or myelodysplastic neoplasms post-allotransplant. However, the underlying mechanism by which BM EPCs regulate their intracellular ROS levels and the capacity to support hematopoiesis have not been well clarified. Herein, we demonstrated decreased levels of peroxisome proliferator-activated receptor delta (PPARδ), a lipid-activated nuclear receptor, in BM EPCs of PGF patients compared with those with good graft function (GGF). In vitro assays further identified that PPARδ knockdown contributed to reduced and dysfunctional BM EPCs, characterized by the impaired ability to support hematopoiesis, which were restored by PPARδ overexpression. Moreover, GW501516, an agonist of PPARδ, repaired the damaged BM EPCs triggered by 5-fluorouracil (5FU) in vitro and in vivo. Clinically, activation of PPARδ by GW501516 benefited the damaged BM EPCs from PGF patients or acute leukemia patients in complete remission (CR) post-chemotherapy. Mechanistically, we found that increased expression of NADPH oxidases (NOXs), the main ROS-generating enzymes, may lead to elevated ROS level in BM EPCs, and insufficient PPARδ may trigger BM EPC damage via ROS/p53 pathway. Collectively, we found that defective PPARδ contributes to BM EPC dysfunction, whereas activation of PPARδ in BM EPCs improves their hematopoiesis-supporting ability after myelosuppressive therapy, which may provide a potential therapeutic target not only for patients with leukemia but also for those with other cancers.
•PPARδ knockdown contributed to reduced and dysfunctional BM EPCs, which can be restored by PPARδ overexpression.•Activation of PPARδ benefited the damaged BM EPCs from PGF patients or AML-CR patients.•Increased expression of NADPH oxidases (NOXs) may lead to elevated ROS level in BM EPCs.•Insufficient PPARδ may trigger BM EPC damage via ROS/p53 pathway.
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•Methanol can be synthesized from CO/CO2 hydrogenation which is dependent on Cu valence.•CO is the main carbon source when the surface is predominantly covered by Cu+ species.•CO2 is ...the primary carbon source when metallic Cu covers the surface.
A systematic theoretical study was performed to investigate methanol synthesis from CO/CO2 hydrogenation and the water-gas-shift (WGS) reaction on Cu(111) and Cu2O(111) surfaces using density functional theory (DFT) and kinetic Monte Carlo (KMC) simulations. Specifically, DFT was used to investigate methanol synthesis from CO/CO2 hydrogenation on these surfaces at P=80atm, T=553K and (CO+ CO2)/H2=20/80. The results show that methanol can be synthesized from CO or CO2 hydrogenation and is dependent on the catalyst’s preparation as well as the active site type. Further, CO is the main carbon source when the surface is predominantly covered by Cu+ species. However, CO2 is the primary carbon source when metallic Cu covers the surface. Under the reaction conditions investigated, H2 and CO easily reduce Cu2O to metallic Cu, and the Cu+ species are stabilized by the presence of H2O, CO2, carrier (such as MgO) or alkali metals. For this reason, the scale of methanol produced from CO or CO2 hydrogenation depends on the ratio of Cu+/Cu0.
Purpose
Although some parameters of positron emission tomography with
18
F-fluorodeoxyglucose (
18
F-FDG) and computed tomography (PET-CT) are somehow helpful in differentiating malignant pleural ...effusion (MPE) from benign effusions, no individual parameter offers sufficient evidence for its implementation in the clinical practice. The aim of this study was to establish the diagnostic accuracy of a scoring system based on PET-CT (the PET-CT score) in diagnosing MPE.
Methods
One prospective derivation cohort of patients with pleural effusions (84 malignant and 115 benign) was used to develop the PET-CT score for the differential diagnosis of malignant pleural effusion. The PET-CT score was then validated in another independent prospective cohort (
n
= 74).
Results
The PET-CT parameters developed for discriminating MPE included unilateral lung nodules and/or masses with increased
18
F-FDG uptake (3 points); extrapulmonary malignancies (3 points); pleural thickening with increased
18
F-FDG uptake (2 points); multiple nodules or masses (uni- or bilateral lungs) with increased
18
F-FDG uptake (1 point); and increased pleural effusion
18
F-FDG uptake (1 point). With a cut-off value of 4 points in the derivation cohort, the area under the curve, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of the PET-CT score to diagnose MPE were 0.949 (95% CI: 0.908–0.975), 83.3% (73.6%–90.6%), 92.2% (85.7%–96.4%), 10.7 (5.6–20.1), and 0.2 (0.1–0.3), respectively.
Conclusions
A simple-to-use PET-CT score that uses PET-CT parameters was developed and validated. The PET-CT score can help physicians to differentiate MPE from benign pleural effusions.
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