A Unique Approach: Biomimetic Graphdiyne-Based Nanoplatform to Treat Prostate Cancer by Combining Cuproptosis and Enhanced Chemodynamic Therapy.

Purpose: Current treatment approaches for Prostate cancer (PCa) often come with debilitating side effects and limited therapeutic outcomes. There is urgent need for an alternative effective and safe treatment for PCa. Methods: We developed a nanoplatform to target prostate cancer cells based on graphdiyne (GDY) and a copper-based metal-organic framework (GDY-CuMOF), that carries the chemotherapy drug doxorubicin (DOX) for cancer treatment. Moreover, to provide GDY-CuMOF@DOX with homotypic targeting capability, we coated the PCa cell membrane (DU145 cell membrane, DCM) onto the surface of GDY-CuMOF@DOX, thus obtaining a biomimetic nanoplatform (DCM@GDY-CuMOF@DOX). The nanoplatform was characterized by using transmission electron microscope, atomic force microscope, X-ray diffraction, etc. Drug release behavior, antitumor effects in vivo and in vitro, and biosafety of the nanoplatform were evaluated. Results: We found that GDY-CuMOF exhibited a remarkable capability to load DOX mainly through π-conjugation and pore adsorption, and it responsively released DOX and generated Cu+ in the presence of glutathione (GSH). In vivo experiments demonstrated that this nanoplatform exhibits remarkable cell-killing efficiency by generating lethal reactive oxygen species (ROS) and mediating cuproptosis. In addition, DCM@GDY-CuMOF@DOX effectively suppresses tumor growth in vivo without causing any apparent side effects. Conclusion: The constructed DCM@GDY-CuMOF@DOX nanoplatform integrates tumor targeting, drug-responsive release and combination with cuproptosis and chemodynamic therapy, offering insights for further biomedical research on efficient PCa treatment.

The chest X-ray score baseline in predicting continuous oxygen therapy failure in low-risk aged patients after thoracic surgery.

Background: Radiographic severity assessment can be instrumental in diagnosing postoperative pulmonary complications (PPCs) and guiding oxygen therapy. The radiographic assessment of lung edema (RALE) and Brixia scores correlate with disease severity, but research on low-risk elderly patients is lacking. This study aimed to assess the efficacy of two chest X-ray scores in predicting continuous oxygen therapy (COT) treatment failure in patients over 70 years of age after thoracic surgery. Methods: From January 2019 to December 2021, we searched for patients aged 70 years and above who underwent thoracic surgery and received COT treatment, with a focus on those at low risk of respiratory complications. Bedside chest X-rays, RALE, Brixia scores, and patient data were collected. Univariate, multivariate analyses, and 1:2 matching identified risk factors. Receiver operating characteristic (ROC) curves determined score sensitivity, specificity, and predictive values. Results: Among the 242 patients surviving to discharge, 19 (7.9%) patients experienced COT failure. COT failure correlated with esophageal cancer surgeries, thoracotomies (36.8% vs. 9%, P=0.003; 26.3% vs. 9.4%, P=0.004), and longer operation time (3.4 vs. 2.8 h, P=0.003). Surgical approach and RALE score were independent risk factors. The prediction model had an area under the curve (AUC) of 0.839 [95% confidence interval (CI), 0.740-0.938]. Brixia and RALE scores predicted COT failure with AUCs of 0.764 (95% CI, 0.650-0.878) with a cut-off value of 6.027 and 0.710 (95% CI, 0.588-0.832) with a cut-off value of 17.134, respectively, after 1:2 matching. Conclusions: The RALE score predict the risk of COT failure in elderly, low-risk thoracic patients better than the Brixia score. This simple, cheap, and noninvasive method helps evaluate postoperative lung damage, monitor treatment response, and provide early warning for oxygen therapy escalation. Further studies are required to confirm the validity and applicability of this model in different settings and populations.

Ferrocene-Based Polymeric Nanoparticles Carrying Doxorubicin for Oncotherapeutic Combination of Chemotherapy and Ferroptosis.

Mono-chemotherapy has significant side effects and unsatisfactory efficacy, limiting its clinical application. Therefore, a combination of multiple treatments is becoming more common in oncotherapy. Chemotherapy combined with the induction of ferroptosis is a potential new oncotherapy. Furthermore, polymeric nanoparticles (NPs) can improve the antitumor efficacy and decrease the toxicity of drugs. Herein, a polymeric NP, mPEG-b-PPLGFc@Dox, is synthesized to decrease the toxicity of doxorubicin (Dox) and enhance the efficacy of chemotherapy by combining it with the induction of ferroptosis. First, mPEG-b-PPLGFc@Dox is oxidized by endogenous H2 O2 and releases Dox, which leads to an increase of H2 O2 by breaking the redox balance. The Fe(II) group of ferrocene converts H2 O2 into ·OH, inducing subsequent ferroptosis. Furthermore, glutathione peroxidase 4, a biomarker of ferroptosis, is suppressed and the lipid peroxidation level is elevated in cells incubated with mPEG-b-PPLGFc@Dox compared to those treated with Dox alone, indicating ferroptosis induction by mPEG-b-PPLGFc@Dox. In vivo, the antitumor efficacy of mPEG-b-PPLGFc@Dox is higher than that of free Dox. Moreover, the loss of body weight in mice treated mPEG-b-PPLGFc@Dox is lower than in those treated with free Dox, indicating that mPEG-b-PPLGFc@Dox is less toxic than free Dox. In conclusion, mPEG-b-PPLGFc@Dox not only has higher antitumor efficacy but it reduces the damage to normal tissue.

A postoperative comparison of high-flow nasal cannula therapy and conventional oxygen therapy for esophageal cancer patients.

BACKGROUND: Hypoxaemia in post-surgical patients of esophageal cancer (EC) is common in thoracic departments. However, few studies have investigated the role of high-flow nasal cannula (HFNC) compared with conventional oxygen therapy (COT). METHODS: A retrospective study was implemented to enroll hypoxemic patients after esophagectomy who were treated by HFNC or COT immediately after extubation between January 2019 and December 2019. We compared the effect of HFNC or COT in patients regarding the vital signs and arterial blood gases, the incidence of anastomotic leakage, postoperative pulmonary complications (PPCs), sore throat/nose, and reintubation, length of stay, and sputum production. We also 3D reconstructed the postoperative chest CT, and compared the amount of lung volume loss caused by PPCs (pneumothorax, atelectasis, pulmonary consolidation and pleural effusion) between the two groups. RESULTS: Compared to patients in COT group, sore throat/nose in HFNC group was lower, the sputum production was higher, and the total hospital stay was shorter. Compared to COT, HFNC treatment decreased systolic blood pressure (SBP) at day 1, diastolic blood pressure (DBP) at day 1-4, and heart rate (HR) at day 2-4, increased arterial partial pressure of oxygen (PaO2) at day 1-4, and arterial oxygen saturation (SaO2%) at day 1-2. In addition, the rate of PPCs and anastomotic leakage in HFNC group were lower than those in COT group. Compared to COT, HFNC treatment significantly decreased the amount of lung volume loss caused by PPCs. CONCLUSIONS: HFNC can improve the hypoxemia of patients after esophagectomy, increase the flow of sputum, reduce the incidence of PPC and anastomotic leakage.

Singlet oxygen generation on porous superhydrophobic surfaces: effect of gas flow and sensitizer wetting on trapping efficiency.

We describe physical-organic studies of singlet oxygen generation and transport into an aqueous solution supported on superhydrophobic surfaces on which silicon-phthalocyanine (Pc) particles are immobilized. Singlet oxygen ((1)O2) was trapped by a water-soluble anthracene compound and monitored in situ using a UV-vis spectrometer. When oxygen flows through the porous superhydrophobic surface, singlet oxygen generated in the plastron (i.e., the gas layer beneath the liquid) is transported into the solution within gas bubbles, thereby increasing the liquid-gas surface area over which singlet oxygen can be trapped. Higher photooxidation rates were achieved in flowing oxygen, as compared to when the gas in the plastron was static. Superhydrophobic surfaces were also synthesized so that the Pc particles were located in contact with, or isolated from, the aqueous solution to evaluate the relative effectiveness of singlet oxygen generated in solution and the gas phase, respectively; singlet oxygen generated on particles wetted by the solution was trapped more efficiently than singlet oxygen generated in the plastron, even in the presence of flowing oxygen gas. A mechanism is proposed that explains how Pc particle wetting, plastron gas composition and flow rate as well as gas saturation of the aqueous solution affect singlet oxygen trapping efficiency. These stable superhydrophobic surfaces, which can physically isolate the photosensitizer particles from the solution may be of practical importance for delivering singlet oxygen for water purification and medical devices.