Codelivery of Dual Gases with Metal-Organic Supramolecular Cage-Based Microenvironment-Responsive Nanomedicine for Atherosclerosis Therapy.

Atherosclerosis (AS) is a common cause of coronary heart disease and stroke. The delivery of exogenous H2S and in situ production of O2 within atherosclerotic plaques can help suppress inflammatory cell infiltration and alleviate disease progression. However, the uncontrolled release of gas donors hinders achieving effective drug concentrations and causes toxic effects. Herein, diallyl trisulfide (DATS)-loaded metal-organic cage (MOC)-68-doped MnO2 nanoparticles are developed as a microenvironment-responsive nanodrug with the capacity for the in situ co-delivery of H2S and O2 to inflammatory cells within plaques. This nanomedicine exhibited excellent monodispersity and stability and protected DATS from degradation in the circulation. In vitro studies showed that the nanomedicine reduced macrophage polarization toward an inflammatory phenotype and inhibited the formation of foam cells, while suppressing the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and interleukin-1ß. In a mouse model of ApoE-/- genotype, the nanomedicine reduces the plaque burden, inflammatory infiltration, and hypoxic conditions within the plaques. Furthermore, the treatment process and therapeutic effects can be monitored by magnetic resonance image (MRI), in real time upon Mn2+ release from the acidic- and H2O2- microenvironment-responsive MnO2 nanoparticles. The DATS-loaded MOC-68-doped MnO2-based nanodrug holds great promise as a novel theranostic platform for AS.

Trajectory patterns and influencing factors of supportive care needs in stroke patients: A longitudinal study.

AIM: To investigate the trajectory patterns and influencing factors of supportive care needs in stroke patients. DESIGN: A longitudinal study. METHODS: In total, 207 stroke patients who received treatment at the Department of Neurology in a hospital in Xuzhou between July 2022 and July 2023 were recruited using convenience sampling. Questionnaires including supportive care needs, hospital anxiety and depression scale, and the Barthel index were investigated at baseline and at 1, 3, and 6 months. A latent class growth model was applied to identify the supportive care needs trajectories. Multiple logistic regression was used to determine the predictors for membership. This study adheres to STROBE reporting guidelines. RESULTS: Three patterns of supportive care needs trajectories were identified: A high needs slow decline group (20.8%), a medium needs stable group (56.5%) and a medium needs rapid decline group (22.7%). Based on further analysis, the findings indicated that age, education level, monthly income, comorbidity, activities of daily living, anxiety and depression were associated with the trajectory categories of supportive care needs with stroke patients. CONCLUSION: This study demonstrates heterogeneity in changes in supportive care needs among stroke patients. Healthcare providers need to consider these different categories of needs and develop individualized care measures based on the characteristics of different patients. IMPACT: Healthcare providers should be aware of the fluctuations in care needs of stroke patients at various stages. Additionally, the study aimed to identify patients' specific needs based on their circumstances, monitor the rehabilitation process and establish a more personalized and optimized care plan through multidisciplinary collaboration. The ultimate goal was to alleviate symptomatic distress and address the long-term care needs of patients. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Systematic Evaluation of Guidelines for the Diagnosis and Treatment of Hepatitis E Virus Infection.

Background and Aims: The hepatitis E virus (HEV) is a zoonotic disease, and infection with HEV in humans primarily causes acute infections and can progress to chronic manifestation in immunocompromised individuals. Over the past decade, guidelines for diagnosing and treating HEV infection have been developed. This study aimed to systematically assess the quality of current guidelines for diagnosing and treating HEV infection, and we analyzed the differences in guideline quality and primary recommendations and explored possible reasons for these differences. Methods: Guidelines published between 2013 and 2022 were searched, and studies were identified using selection criteria. The study assessed the quality of the included guidelines using the Appraisal of Guidelines for Research and Evaluation tool, extracted the primary recommendations in the guidelines, determined the highest level of evidence supporting the recommendations, and reclassified the evidence using the Oxford Centre for Evidence-Based Medicine grading system. Results: Seven guidelines were included in the final analysis. The quality of the guidelines varied widely. The discrepancies may have been caused by the lack of external experts, the failure to consider influencing factors in guideline application, and the lack of consideration of the public's opinion. Analysis of the heterogeneity in primary recommendations revealed differences in algorithms for managing chronic HEV infection, the dosage of ribavirin, and a low level of evidence supporting the primary recommendations. Conclusions: Guideline quality and primary recommendations vary considerably. Refinement by guideline developers and researchers would facilitate updating and applying guidelines for diagnosing and treating HEV infection.

Quantification of the Engraftment Status of Mesenchymal Stem Cells in Glioma Using Dual-Modality Magnetic Resonance Imaging and Bioluminescence Imaging.

RATIONALE AND OBJECTIVES: The tumor-tropic properties of mesenchymal stem cells (MSCs) enable them to serve as appealing cellular vehicles for delivering therapeutic agents to treat malignant glioma. However, the exact engraftment status of MSCs in glioma via different administration routes remains unclear due to the lack of quantitative analysis. This study aimed to quantify the engraftment of MSCs in glioma after administration via different routes using non-invasive dual-modality magnetic resonance imaging (MRI) and bioluminescence imaging (BLI). MATERIALS AND METHODS: MSCs were transduced with a lentivirus overexpressing ferritin heavy chain (FTH) and firefly luciferase (FLUC) reporter genes to yield FTH- and FLUC-overexpressed MSCs (FTH-FLUC-MSCs). Wistar rats bearing intracranial C6 glioma received peritumoral, intratumoral, intra-arterial, and intravenous injection of FTH-FLUC-MSCs, respectively. MRI and BLI were performed to monitor FTH-FLUC-MSCs in vivo. RESULTS: FTH-FLUC-MSCs administered via peritumoral, intratumoral and intra-arterial routes migrated specially toward the intracranial glioma in vivo, as detected by MRI and BLI. As quantified by the BLI signal intensity, the percentages of FTH-FLUC-MSCs in the glioma were significantly higher with peritumoral injection (61%) and intratumoral injection (71%) compared to intra-arterial injection (30%) and intravenous injection (0%). Peritumorally injected FTH-FLUC-MSCs showed a gradual decline, with approximately 6% of FTH-FLUC-MSCs still retained within the tumor up to 11 days after injection. Meanwhile, the number of FTH-FLUC-MSCs injected via other routes dropped quickly, and none were detectable by day 11 post-injection. CONCLUSION: Peritumoral delivery of FTH-FLUC-MSCs offers robust engraftment and could be used as the optimal delivery route for treating malignant glioma.