Effects of online-offline integrated death education on patients with advanced cancer: A before-and-after study.

PURPOSE: To evaluate the effectiveness of the constructed OOIDE intervention in patients with advanced cancer. METHOD: In this study, patients were invited to participate in a 4-week OOIDE intervention. The assessment of patients' ability to cope with death was conducted using a scale in conjunction with interviews. Additionally, patients' 'readiness to die' was assessed. RESULTS: Thirty-two patients with advanced cancer participated in this study. Our intervention significantly enhanced their perspective on life and spirituality, while also reducing their fear of death (P < 0.01). Furthermore, it facilitated their acceptance of death, encouraged a more rational approach to their illness, and fostered an understanding of hospice care, thereby reinforcing their sense of self-worth. Additionally, the intervention improved the relationship between the patient and their families, fostering greater mutual understanding and respect for the patient's perspectives. Comparing the results to the pre-intervention period, there was a significant increase in the number of patients who discussed death with their families and contemplated the place of their passing (P < 0.05). CONCLUSION: OOIDE improves participants' ability to confront death, while also assisting patients' families in the physical and psychological preparations for the loss of their relative.

On-chip gas reaction nanolab for in situ TEM observation.

The catalysis reaction mechanism at nano/atomic scale attracted intense attention in the past decades. However, most in situ characterization technologies can only reflect the average information of catalysts, which leads to the inability to characterize the dynamic changes of single nanostructures or active sites under operando conditions, and many micro-nanoscale reaction mechanisms are still unknown. The combination of in situ transmission electron microscopy (TEM) holder system with MEMS chips provides a solution for it, where the design and fabrication of MEMS chips are the key factors. Here, with the aid of finite element simulation, an ultra-stable heating chip was developed, which has an ultra-low thermal drift during temperature heating. Under ambient conditions within TEM, atomic resolution imaging was achieved during the heating process or at high temperature up to 1300 °C. Combined with the developed polymer membrane seal technique and nanofluidic control system, it can realize an adjustable pressure from 0.1 bar to 4 bar gas environment around the sample. By using the developed ultra-low drift gas reaction cells, the nanoparticle's structure evolution at atomic scale was identified during reaction.

Novel ester tethered dihydroartemisinin-3-(oxime/thiosemicarbazide)isatin hybrids as potential anti-breast cancer agents: Synthesis, in vitro cytotoxicity and structure-activity relationship.

A series of ester tethered dihydroartemisinin-3-(oxime/thiosemicarbazide)isatin hybrids 7a-p were designed, synthesized, and assessed for their antiproliferative activity against MCF-7, MDA-MB-231, MCF-7/ADR, and MDA-MB-231/ADR breast cancer cell lines. Among them, hybrids 7a,f (IC50 : 1.33-3.84 µM) showed potent activity against triple-negative (MDA-MB-231 and MDA-MB-231/ADR) breast cancer cell lines, and hybrid 7f (IC50 : 3.90 and 10.18 µM) also demonstrated promising activity against estrogen receptor-positive breast cancer cells (MCF-7 and MCF-7/ADR), and the activity was superior to these of artemisinin, dihydroartemisinin, and ADR, revealing their potential to fight against both drug-sensitive and drug-resistant breast cancers. The enriched structure-activity relationships may facilitate further design of more active candidates.

Design, synthesis, and in vitro cytotoxicity evaluation of novel dihydroartemisinin-isatin hybrids tethered via different length of esters as potential anti-breast cancer agents.

In the present work, we reported the design, synthesis, and in vitro cytotoxicity evaluation of novel dihydroartemisinin-isatin hybrids tethered via different length of esters against MCF-7, MDA-MB-231, MCF-7/ADR and MDA-MB-231/ADR breast cancer cell lines. The preliminary results showed that the majority of the hybrids exhibited good anti-breast cancer cell activity. In particular, hybrids 7 g and 7n not only were more potent than ART, DHA and ADR against the four tested breast cancer cell lines, but also were non-toxic towards normal MCF-10A breast cells. The selectivity index values of hybrids 7 g and 7n were > 12.83 and > 25.97 respectively, revealing their excellent safety and selectivity profiles. The drug-resistant index values of hybrids 7 g and 7n were in a range of 0.33 to 1.12, implying that these hybrids had the potential to overcome drug resistance. Accordingly, hybrids 7 g and 7n could be considered as potential lead molecules for the development of novel anti-breast cancer agents with minimal untoward events to normal human cells. The structure-activity relationships indicated that the length of ester likner between DHA and isatin as well as substituents at C-3 and C-5 positions of isatin moiety had great impact on the activity.

Ocular and systemic pharmacokinetics of BI-X, a nanobody targeting VEGF and Ang-2, after intravitreal dosing in cynomolgus monkeys - Evidence for half-life extension by albumin.

Half-life extension strategies to reduce the intravitreal dosing frequency of biomolecules for the treatment of retinal neovascular diseases are attracting increasing interest. This study investigated ocular and systemic pharmacokinetics of the trivalent nanobody BI-X (with affinity to VEGF, Ang-2 and human albumin) in cynomolgus monkeys after intravitreal injection. BI-X concentrations were measured in serial samples of plasma, vitreous humor, aqueous humor and retina. Ocular pharmacokinetics of BI-X exhibited two phases. Initially up to 2-4 weeks after dosing, BI-X concentrations in vitreal, aqueous humor and retina declined with half-lives of around 3 days, which is comparable to macromolecules with a similar molecular weight. Thereafter, only vitreal concentrations were measurable, with a terminal half-life of 13.2 days, which is considerably longer than expected based on the BI-X molecular weight or hydrodynamic radius. It is hypothesized that binding of BI-X to low levels of intraocular albumin resulted in this half-life extension. BI-X was detectable in plasma up to 10 weeks post-dosing. Plasma pharmacokinetics of BI-X exhibited a similar biphasic disposition profile to the vitreous body, with a terminal half-life of 11.8 days, thus reflecting input kinetics from the eye. In conclusion, an important half-life extension principle based on vitreal albumin binding could be confirmed in a primate model, and the data obtained can potentially be translated to humans taking into account the differing vitreal albumin concentrations.