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Purpose Ventilator-induced lung injury (VILI) is an additional inflammatory injury caused by mechanical ventilation (MV). This study aimed to determine the effects of microRNA-214 (miR-214) on VILI and its underlying mechanism of action. Methods To develop a VILI mouse model, mice were subjected to MV. The expression of miR-214 was detected by qRT-PCR. The macrophages, fibroblasts, epithelial cells, and endothelial cells were isolated from lung tissues by fluorescence-activated cell sorting. The histopathological changes of lung, lung wet/dry weight (W/D) ratio, and myeloperoxidase (MPO) activity were used to evaluate the degree of lung injury. The levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assay was performed to determine the interactions between miR-214 and FGFR1. Western blot was used to detect the protein expression of FGFR1, p-AKT, and p-PI3K. Results The expression of miR-214 was increased in lung tissues and macrophages, fibroblasts, epithelial cells, and endothelial cells isolated from lung tissues in VILI mice. MiR-214 inhibition decreased the histopathological changes of lung, lung W/D ratio, MPO activity, and pro-inflammatory cytokines levels in BALF in VILI mice. FGFR1 was targeted by miR-214. The protein expression of FGFR1 was decreased in VILI mice. Ponatinib (FGFR1 inhibitor) reversed the suppressive effects of miR-214 inhibition on lung injury and inflammation of VILI mice. MiR-214 increased the activity of PI3K/AKT pathway by regulating FGFR1. Conclusions Inhibition of miR-214 attenuated lung injury and inflammation in VILI mice by increasing FGFR1 expression, providing a novel therapeutic target for VILI., Author(s): Kun He [sup.1], Shuang Han [sup.2], Li An [sup.1], Jin Zhang [sup.1] Author Affiliations: (1) Department of Anesthesiology, The Fourth Hospital of Shijiazhuang, , No. 206, Zhongshan East Road, [...]

Background: Patients with transient ischemic attack (TIA) or ischemic stroke demonstrate an increased risk of cognitive dysfunction. Accumulating evidence indicates that ischemic cerebrovascular disease (ICVD) may interact with the amyloid/tau/neurodegeneration (AT[N]) biomarkers to promote dementia. However, the precise pathological mechanisms remain to be fully characterized. Objective: To elucidate the interrelationships among ICVD, ATN biomarkers in cerebrospinal fluid (CSF), and cognition. Methods: A total of 2524 participants were recruited from the CABLE study. ICVD referred to TIA/ischemic stroke. Cognitive performance was assessed by China Modified Mini-Mental State Examination (CM-MMSE) and Montreal Cognitive Assessment-b (MoCA-b). Multivariate linear regression analyses were performed to evaluate the associations of ICVD with CSF ATN biomarkers and cognition. Causal mediation analyses were used to identify whether the association was mediated by ATN biomarkers. Results: ICVD was associated with higher total-tau (t-tau) (p = 2.828×10–2) and poorer cognition (CM-MMSE: p = 1.539×10–5, MoCA-b: p = 4.552×10–6). Additionally, no discernible correlation surfaced between ICVD and amyloid-β (Aβ) 42 (p = 6.910×10–1) or phosphorylated tau (p-tau) (p = 4.324×10–1). The influence of ICVD on cognitive function was partially mediated by CSF t-tau (CM-MMSE: proportion: 2.74%, MoCA-b: proportion: 2.51%). Subgroup analyses revealed the influences of t-tau were especially evident in male (CM-MMSE: proportion: 5.45%, MoCA-b: proportion: 5.38%) and mid-life group (CM-MMSE: proportion: 9.83%, MoCA-b: proportion: 5.31%). Conclusions: These results delineated t-tau as a potential mediator for the influence of ICVD on cognition. Targeting brain ischemia and alleviating neuronal injury induced by ischemia may be a promising approach for preventing cognitive decline. [ABSTRACT FROM AUTHOR]

This systematic review and meta‐analysis evaluate the impact of ultrasound‐guided subsheath versus extrasheath sciatic nerve blocks on postoperative wound pain in tibial and foot surgeries, crucial for effective pain management and patient recovery. Adhering to PRISMA guidelines, this study used a PICO framework, focusing on patients undergoing tibial and foot surgeries and comparing the efficacy and safety of subsheath and extrasheath sciatic nerve blocks. The literature search spanned four databases without time restrictions, assessing various outcomes like success rate, onset time, duration of analgesia and complication rates. Quality assessment employed the Cochrane Collaboration's risk of bias tool, and statistical analyses included heterogeneity assessment, fixed‐effect and random‐effects models, sensitivity analysis and publication bias evaluation using funnel plots and Egger's linear regression test. From an initial pool of 1213 articles, six met the inclusion criteria. The subsheath group showed a significantly higher success rate of complete sensory blockade within 30 min compared with the extrasheath group (OR = 5.39; 95% CI: 2.82–10.28; p < 0.01). No significant differences were found in procedure duration or incidence of nerve‐related complications between the two techniques. The subsheath approach also demonstrated a quicker onset time of sensory blockade (MD = −8.57; 95% CI: −11.27 to −5.88; p < 0.01). Sensitivity analysis confirmed the stability of the results, and no significant publication bias was detected. Ultrasound‐guided subsheath sciatic nerve blocks are more effective than extrasheath blocks in achieving rapid and complete sensory blockade for tibial and foot surgeries, with a quicker onset time and comparable safety profile. Subsheath injections are thus recommended as a preferred method for anaesthesia and postoperative pain management in these surgical procedures, enhancing overall patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Frailty is a vulnerability state increasing the risk of many adverse health outcomes, but little is known about the effects of frailty on neuropsychiatric health. Objective: To explore the associations between frailty and the risk of neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD), especially in its different clinical stages. Methods: We included 2,155 individuals assessed using modified frailty index-11 (mFI-11), Neuropsychiatric Inventory (NPI) and Neuropsychiatric Inventory Questionnaire (NPI-Q) in the Alzheimer's Disease Neuroimaging Initiative (ADNI). The relationships between frailty and NPSs were explored with logistic regression models and Cox proportional hazard regression models. Causal mediation analyses were conducted to explore the mediation factors between frailty and NPSs. Results: Among mild cognitive impairment (MCI) participants, frailty was cross-sectionally associated with an increased risk of apathy, and longitudinally associated with increased risk of depression and apathy. Among AD participants, frailty was cross-sectionally associated with increased risk of depression and anxiety, and longitudinally associated with an increased risk of apathy. Among participants with cognitive progression, frailty was associated with increased risk of depression and apathy. In MCI participants, the influence of frailty on NPSs was partially mediated by hippocampus volume, whole brain volume, and monocytes, with mediating proportions ranging from 8.40% to 9.29%. Conclusions: Frailty was associated with NPSs such as depression, anxiety, and apathy among MCI, AD, and cognitive progression participants. Atrophy of the hippocampus and whole brain, as well as peripheral immunity may be involved in the potential mechanisms underlying the above associations. [ABSTRACT FROM AUTHOR]

Three new compounds (1–2, 4) along with ten known ones (3, 5–13), were isolated from the whole plant of Erigeron breviscapus. Compounds 1 and 2, two novel C10 acetylenic acids and compound 4, a jasmone glucoside were elucidated by the detailed analysis of 1D and 2D NMR, HRESIMS spectra, and experimental and calculated electronic circular dichroism (ECD). Compounds 1–3 represent the first example of acetylenic acids incorporating C10 skeleton from E. breviscapus. In addition, the antioxidant effects of all compounds were evaluated by ferric reducing power, 2,2′-Azinobis-(3-ethylbenzthiazoline-6-sulphonate acid) (ABTS) and 2.2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays. Our results indicated the significant antioxidant activity of caffeoylquinic acids. Additionally, compounds 10–11 and 13 played protective role on alcoholic liver injury cells in a dose-dependent manner. [ABSTRACT FROM AUTHOR]