Background: As a chronic and progressive neurodegenerative disease, Parkinson's disease (PD) still lacks effective and safe targeted drug therapy. Low-intensity focused ultrasound (LIFU), a new method to stimulate the brain and open the blood-brain barrier (BBB), has been widely concerned by PD researchers due to its non-invasive characteristics.Methods: PubMed was searched for the past 10 years using the terms 'focused ultrasound', 'transcranial ultrasound', 'pulse ultrasound', and 'Parkinson's disease'. Relevant citations were selected from the authors' references. After excluding articles describing high-intensity focused ultrasound or non-Parkinson's disease applications, we found more than 100 full-text analyses for pooled analysis.Results: Current preclinical studies have shown that LIFU could improve PD motor symptoms by regulating microglia activation, increasing neurotrophic factors, reducing oxidative stress, and promoting nerve repair and regeneration, while LIFU combined with microbubbles (MBs) can promote drugs to cross the BBB, which may become a new direction of PD treatment. Therefore, finding an efficient drug carrier system is the top priority of applying LIFU with MBs to deliver drugs.Conclusions: This article aims to review neuro-modulatory effect of LIFU and the possible biophysical mechanism in the treatment of PD, summarize the latest progress in delivering vehicles with MBs, and discuss its advantages and limitations.

Objective: Parkinson’s disease (PD) is associated with dysregulated neural cell death, such as pyroptosis, but its regulatory mechanisms are poorly understood. This study investigated roles of nuclear factor E2-related factor 2 (Nrf2) in regulating pyroptosis and PD development. Methods: Cellular and rat PD models established by 6-OHDA exposure were subjected to Nrf2 overexpression. Neurobehavioral functions were assessed by the traction test, Morris Water Maze, and open field test. Cell proliferation was analyzed by MTS assay, while flow cytometry was applied to quantify levels of reactive oxygen species (ROS) and apoptosis. Nissl bodies in rat brains were detected by Nissl staining, and cell apoptosis in brain tissues was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling. Differential expression of lncRNA and mRNA was characterized by deep sequencing. Results: A cellular PD model was successfully established by inducing PC12 cell differentiation with nerve growth factor-β and exposing differentiated cells to 6-OHDA. Cells exhibited significantly increased ROS levels, enhanced pyroptosis, and inhibited Nrf2 phosphorylation. The rat PD model exhibited impaired muscle strength, increased pyroptosis, and repressed Nrf2 phosphorylation. Nrf2 overexpression effectively repressed pyroptosis in both cellular and rat PD models. Marked alterations of lncRNA and mRNA profiles were induced by Nrf2 overexpression in the cellular PD model, which involved multiple signaling pathways. Silencing of the lncRNA AABR07032261.5 significantly promoted pyroptosis in the cellular PD model. Conclusion: Nrf2 suppressed PD pathogenesis in cellular and animal models by promoting AABR07032261.5, which repressed pyroptosis.

Background: Recurrent fever of unknown origin (FUO) poses a significant diagnostic challenge. While nutritional deficiencies, particularly of vitamin D, are recognized for their immunomodulatory roles, their potential as a plausible contributing factor of recurrent fever remains underappreciated. This case report aims to describe the resolution of recurrent fever after vitamin D repletion. Case presentation: A 52-year-old woman presented with a one-month history of recurrent high-grade fever (peak 39.4 °C), leukopenia, anemia, and systemic symptoms. An exhaustive diagnostic workup was performed to exclude infectious, autoimmune, and neoplastic etiologies. Comprehensive investigations, including metagenomic sequencing of cerebrospinal fluid, ruled out common FUO etiologies. A subsequent nutritional assessment revealed the underlying cause——severe vitamin D deficiency (25-hydroxyvitamin D: 8.7 nmol/L, equivalent to 3.48 ng/mL), attributed to insufficient sun exposure. Upon initiation of oral vitamin D supplementation, the patient’s fever resolved entirely. No recurrence was observed during an 18-month follow-up period, coinciding with the normalization of her vitamin D levels. Conclusions: This case identifies severe vitamin D deficiency as an underrecognized potential contributing factor of recurrent fever. It underscores the critical importance of integrating nutritional assessment, specifically vitamin D status evaluation, into the standard diagnostic algorithm for FUO. This approach may contribute to targeted treatment and should be considered as a complementary component of the comprehensive FUO diagnostic workup.

Many studies reported impairment of working memory performance in Parkinson's disease (PD) patients. However, it is largely unknown whether different characteristics of the memory items could affect the performance of visual working memory in PD patients. In this study, we employed two types of stimuli - real-world objects and Gestalt organization, which may primarily evoke top-down modulation of high-level cognitive functions and bottom-up processing of low-level visual function, respectively, to investigate their effects on visual working memory performance in patients with PD compared to healthy controls. Experiment 1 used real-world objects and simple color blocks as memory materials, and we found that the overall memory performance of the PD group and the control group showed deficits for real objects compared to simple colors. While healthy individuals showed deficits only under high memory load, PD patients experienced difficulties for memorizing real-world object even under low memory load, indicating a reduction in visual working memory capacity. Experiment 2 used Gestalt illusory contours as memory materials, and it showed that PD patients obtain the memory gain of Gestalt organization when memorizing task-relevant orientations rather than task-irrelevant colors, indicating that the memory benefits are acquired when the features constituting illusory are relevant to the task. Our findings suggest that PD patients do not benefit from top-down modulation induced by memorizing real-world objects, but can improve through Gestalt organization, indicating that bottom-up perceptual grouping remains intact in PD and revealing a functional divergence between low-level and high-level visual and cognitive abilities in PD.

Background The impact of chemotherapy on cardiocerebrovascular disease (CCVD) outcomes in patients with colorectal cancer (CRC) remains insufficiently explored. This research aimed to clarify the association between chemotherapy and CCVD-related mortality in middle-aged and elderly CRC patients. Methods CRC patients aged ≥ 50 years at diagnosis were identified from the Surveillance, Epidemiology, and End Results (SEER) database for the period 2010–2015. The primary outcome was CCVD-related mortality. Survival analyses included Kaplan-Meier (KM) curves to characterize CCVD-related survival patterns and multivariate competing risks regression analysis to evaluate the independent association between chemotherapy and CCVD-related mortality. Subgroup analyses and Fine-Gray competing risks models were additionally performed to enhance the robustness of study findings. Results A total of 136 095 CRC patients were included. KM analysis showed a significantly lower cumulative risk of CCVD-related mortality in chemotherapy treatment group than in non-chemotherapy treatment group. After adjusting for age, race, gender, primary tumor site, and tumor stage, multivariate competing risks regression analysis confirmed that chemotherapy was an independent protective factor against CCVD-related mortality (sHR = 0.75, 95% CI 0.71–0.79, P < 0.001). Subgroup analyses and Fine-Gray competing risks models further validated the robustness of chemotherapy’s beneficial effect on CCVD outcomes. Conclusion Chemotherapy may serve as an independent protective factor against CCVD-related mortality in CRC patients. These findings can help alleviate concerns regarding chemotherapy-associated CCVD risk in CRC management and provide novel insights for clinical decision-making and future research.

To investigate the association between longitudinal sleep duration trajectories and the risk of cardio-renal-metabolic multimorbidity (CRMM) in a populatio