Summary
What is known and objective
Drug fever is frequently misdiagnosed, especially during concurrent infection. Celecoxib causes various adverse effects; however, celecoxib‐induced drug fever is ...rarely reported.
Case summary
A 32‐year‐old man presented with pyrexia after 17 days of celecoxib therapy, which was reintroduced following 3‐day total drug cessation. His fever recurred after this unsuspected rechallenge, which aided in the ultimate identification of the offending drug. A Naranjo Score of 8 led us to infer that drug fever was “probably” caused by celecoxib.
What is new and conclusion
This is the first report of celecoxib‐induced drug fever, aimed at assisting its diagnosis, particularly with rarely suspected causative drugs.
As an anti‐inflammatory drug, celecoxib was not readily suspected as a pyrogen. This is the first report of celecoxib‐induced drug fever, aimed at assisting diagnosis of drug fever, particularly with rarely suspected causative drugs.
Abstract
The emergence of ferromagnetism in two-dimensional van der Waals materials has aroused broad interest. However, the ferromagnetic instability has been a problem remained. In this work, by ...using the first-principles calculations, we identified the critical ranges of strain and doping for the bilayer Cr
2
Ge
2
Te
6
within which the ferromagnetic stability can be enhanced. Beyond the critical range, the tensile strain can induce the phase transition from the ferromagnetic to the antiferromagnetic, and the direction of magnetic easy axis can be converted from out-of-plane to in-plane due to the increase of compressive strain, or electrostatic doping. We also predicted an electron doping range, within which the ferromagnetism can be enhanced, while the ferromagnetic stability was maintained. Moreover, we found that the compressive strain can reverse the spin polarization of electrons at the conduction band minimum, so that two categories of half-metal can be induced by controlling electrostatic doping in the bilayer Cr
2
Ge
2
Te
6
. These results should shed a light on achieving ferromagnetic stability for low-dimensional materials.
ObjectiveThe perioperative chemotherapy with fluorouracil, leucovorin, oxaliplatin plus docetaxel (FLOT) was recommended by the Chinese Society of Clinical Oncology Guidelines for gastric cancer ...(2018 edition) for patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (class IIA). However, the economic impact of FLOT chemotherapy in China remains unclear. The analysis aimed to compare the cost-effectiveness of FLOT versus epirubicin, cisplatin plus fluorouracil or capecitabine (ECF/ECX) in patients with locally advanced resectable tumours.DesignWe developed a Markov model to compare the healthcare and economic outcomes of FLOT and ECF/ECX in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma. Costs were estimated from the perspective of Chinese healthcare system. Clinical and utility inputs were derived from the FLOT4 phase II/III clinical trial and published literature. Sensitivity analyses were employed to assess the robustness of our result. The annual discount rate for costs and health outcomes was set at 5%.Outcome measuresThe primary outcome of incremental cost-effectiveness ratios (ICERs) was calculated as the cost per quality-adjusted life years (QALYs).ResultsThe base-case analysis found that compared with ECF/ECX, the use of FLOT chemotherapy was associated with an additional 1.08 QALYs, resulting in an ICER of US$851/QALY. One-way sensitivity analysis results suggested that the HR of overall survival and progression-free survival had the greatest impact on the ICER. Probabilistic sensitivity analysis demonstrated that FLOT was more likely to be cost-effective compared with ECF/ECX at a willingness-to-pay threshold of US$31 513/QALY.ConclusionsFor patients with locally advanced resectable tumours, the FLOT chemotherapy is a cost-effective treatment option compared with ECF/ECX in China.Trial registration number NCT01216644.
Summary
Atherosclerosis is a chronic inflammatory disease. Recently, a growing body of evidence emphasizes that the monocyte and macrophage differentiation and activation are key processes in the ...development of atherosclerosis. However, the regulatory mechanism that manipulates the function of monocyte and macrophage is still unclear. Recent years, epigenetic mechanisms have received a wide attention and bring us a new field of vision. More and more evidence shows that epigenetics weighs heavily in atherosclerosis by regulating the function and differentiation states of monocyte and macrophage. In this review, we illuminate the epigenetic regulation mechanisms in monocyte and macrophage and their contributions to inflammatory processes of atherosclerosis to provide new thoughts and find novel targets or biomarkers for atherosclerosis.
Temozolomide (TMZ) resistance presents a significant challenge in the treatment of gliomas. Although lysine demethylase 4A (KDM4A) has been implicated in various cancer‐related processes, its role in ...TMZ resistance remains unclear. This study aims to elucidate the contribution of KDM4A to TMZ resistance in glioma cells and its potential implications for glioma prognosis. We assessed the expression of KDM4A in glioma cells (T98G and U251MG) using qRT‐PCR and Western blot assays. To explore the role of KDM4A in TMZ resistance, we transfected siRNA targeting KDM4A into drug‐resistant glioma cells. Cell viability was assessed using the CCK‐8 assay and the TMZ IC50 value was determined. ChIP assays were conducted to investigate KDM4A, H3K9me3, and H3K36me3 enrichment on the promoters of ROCK2 and HUWE1. Co‐immunoprecipitation confirmed the interaction between HUWE1 and ROCK2, and we examined the levels of ROCK2 ubiquitination following MG132 treatment. Notably, T98G cells exhibited greater resistance to TMZ than U251MG cells, and KDM4A displayed high expression in T98G cells. Inhibiting KDM4A resulted in decreased cell viability and a reduction in the TMZ IC50 value. Mechanistically, KDM4A promoted ROCK2 transcription by modulating H3K9me3 levels. Moreover, disruption of the interaction between HUWE1 and ROCK2 led to reduced ROCK2 ubiquitination. Inhibition of HUWE1 or overexpression of ROCK2 counteracted the sensitization effect of si‐KDM4A on TMZ responsiveness in T98G cells. Our findings highlight KDM4A's role in enhancing TMZ resistance in glioma cells by modulating ROCK2 and HUWE1 transcription and expression through H3K9me3 and H3K36me3 removal.
Embryonic stem cells (ESCs) and induced pluripotent stem cells have the potential to differentiate to all cell types of an adult individual and are useful for studying development and for ...translational research. However, extrapolation of mouse and human ESC knowledge to deriving stable ESC lines of domestic ungulates and large livestock species has been challenging. In contrast to ESCs that are usually established from the blastocyst, mouse expanded potential stem cells (EPSCs) are derived from four-cell and eight-cell embryos. We have recently used the EPSC approach and established stem cells from porcine and human preimplantation embryos. EPSCs are molecularly similar across species and have broader developmental potential to generate embryonic and extraembryonic cell lineages. We further explore the EPSC technology for mammalian species refractory to the standard ESC approaches and report here the successful establishment of bovine EPSCs (bEPSCs) from preimplantation embryos of both wild-type and somatic cell nuclear transfer. bEPSCs express high levels of pluripotency genes, propagate robustly in feeder-free culture, and are genetically stable in long-term culture. bEPSCs have enriched transcriptomic features of early preimplantation embryos and differentiate in vitro to cells of the three somatic germ layers and, in chimeras, contribute to both the embryonic (fetal) and extraembryonic cell lineages. Importantly, precise gene editing is efficiently achieved in bEPSCs, and genetically modified bEPSCs can be used as donors in somatic cell nuclear transfer. bEPSCs therefore hold the potential to substantially advance biotechnology and agriculture.
Atherosclerosis has been widely considered as a chronic inflammation process, which triggers a wide range of cardiovascular diseases such as ischemic coronary artery disease (CAD). Toll-like receptor ...4 (TLR4), a primary receptor of the innate immune system, plays a pivotal role in the initiation and progression of atherosclerosis. Here we summarize recent progress on understanding the activation and function of TLR4 signaling in the initiation and development of CAD, with the focus on the role of TLR4 as a link between CAD and other inflammatory diseases. Furthermore, we list a variety of drugs which exert anti-atherosclerosis effects via targeting TLR4 signaling. Finally, we discuss the promise of TLR4 signaling as a therapeutic target for CAD.
•This review highlights the promise of TLR4 signaling as a therapeutic target.•We discuss the role of TLR4 in the initiation and development of atherosclerosis.•A variety of drugs exert anti-atherosclerosis effects via targeting TLR4.•We further provided the possible research direction of TLR4 in the future.
Metabolic hypertension (MH) is the most common type of hypertension worldwide because of unhealthy lifestyles, such as excessive alcohol intake and high-sugar/high-fat diets (ACHSFDs), adopted by ...humans. Poor diets lead to a decrease in the synthesis of short-chain fatty acids (SCFAs), which are produced by intestinal flora and transferred by G protein-coupled receptors (GPCRs), resulting in impaired gastrointestinal function, disrupted metabolic processes, increased blood pressure (BP), and ultimately, MH. It is not clear whether
Dendrobium officinale
polysaccharide (DOPS) can mediate its effects by triggering the SCFAs-GPCR43/41 pathway. In this study, DOPS, with a content of 54.45 ± 4.23% and composition of mannose, glucose, and galacturonic acid at mass percentages of 61.28, 31.87, and 2.53%, was isolated from
Dendrobium officinale
. It was observed that DOPS, given to rats by intragastric administration after dissolution, could lower the BP and improve the abnormal lipid metabolic processes in ACHSFD-induced MH rats. Moreover, DOPS was found to increase the production, transportation, and utilization of SCFAs, while improving the intestinal flora and strengthening the intestinal barrier, as well as increasing the intestinal levels of SCFAs and the expression of GPCR43/41. Furthermore, DOPS improved vascular endothelial function by increasing the expression of GPCR41 and endothelial nitric oxide synthase in the aorta and the nitric oxide level in the serum. However, these effects were all reversed by antibiotic use. These findings indicate that DOPS is the active component of
Dendrobium officinale
, and it can reverse MH in rats by activating the intestinal SCFAs-GPCR43/41 pathway.
Cervical cancer is one of the most common malignant neoplasms in gynecology. Protein tyrosine kinase 7 (PTK7) with an inactive kinase domain is an important regulator of multiple Wnt pathways under ...normal and various pathological conditions and overexpressed in various tumors; however, the clinical and biological significance of PTK7 in cervical cancer is still unknown. In the present study, the protein expression level of PTK7 was detected in clinical cervical cancer patient samples, and the relationship between PTK7 expression and clinicopathological features was analyzed. In addition, the Kaplan-Meier method was performed to estimate the overall survival (OS) and progression-free survival (PFS) of patients to investigate the clinicopathological significance of PTK7 expression. Functional assays demonstrated that knocking down PTK7 might inhibit the ability of cancer cells to proliferate and invade or migrate, both in vivo and in vitro. Thus, PTK7 might serve as a potential target for cervical cancer.
Abstract
Photocatalytic overall water splitting into hydrogen and oxygen is desirable for long-term renewable, sustainable and clean fuel production on earth. Metal sulfides are considered as ideal ...hydrogen-evolved photocatalysts, but their component homogeneity and typical sulfur instability cause an inert oxygen production, which remains a huge obstacle to overall water-splitting. Here, a distortion-evoked cation-site oxygen doping of ZnIn
2
S
4
(D-O-ZIS) creates significant electronegativity differences between adjacent atomic sites, with S
1
sites being electron-rich and S
2
sites being electron-deficient in the local structure of S
1
–S
2
–O sites. The strong charge redistribution character activates stable oxygen reactions at S
2
sites and avoids the common issue of sulfur instability in metal sulfide photocatalysis, while S
1
sites favor the adsorption/desorption of hydrogen. Consequently, an overall water-splitting reaction has been realized in D-O-ZIS with a remarkable solar-to-hydrogen conversion efficiency of 0.57%, accompanying a ~ 91% retention rate after 120 h photocatalytic test. In this work, we inspire an universal design from electronegativity differences perspective to activate and stabilize metal sulfide photocatalysts for efficient overall water-splitting.
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