Cuff-Method Thigh Arterial Occlusion Counteracts Cerebral Hypoperfusion Against the Push–Pull Effect in Humans

Exposure to acute transition from negative (−Gz) to positive (+ Gz) gravity significantly impairs cerebral perfusion in pilots of high-performance aircraft during push—pull maneuver. This push—pull effect may raise the risk for loss of vision or consciousness. The aim of the present study was to explore effective countermeasures against cerebral hypoperfusion induced by the push—pull effect. Twenty healthy young volunteers (male, 21 ± 1 year old) were tested during the simulated push–pull maneuver by tilting. A thigh cuff (TC) pressure of 200 mmHg was applied before and during simulated push—pull maneuver (−0.87 to + 1.00 Gz). Beat-to-beat cerebral and systemic hemodynamics were measured continuously. During rapid −Gz to + Gz transition, mean cerebral blood flow velocity (CBFV) was decreased, but to a lesser extent, in the TC bout compared with the control bout (−3.1 ± 4.9 vs. −7.8 ± 4.4 cm/s, P < 0.001). Similarly, brain-level mean blood pressure showed smaller reduction in the TC bout than in the control bout (−46 ± 12 vs. −61 ± 13 mmHg, P < 0.001). The systolic CBFV was lower but diastolic CBFV was higher in the TC bout. The systemic blood pressure response was blunted in the TC bout, along with similar heart rate increase, smaller decrease, and earlier recovery of total peripheral resistance index than control during the gravitational transition. These data demonstrated that restricting thigh blood flow can effectively mitigate the transient cerebral hypoperfusion induced by rapid shift from −Gz to + Gz, characterized by remarkable improvement of cerebral diastolic flow

Lung ultrasound findings in patients with COVID-19 pneumonia

Since December 2019, the outbreak of pneumonia caused by a new coronavirus [1], which was later identified as coronavirus disease 2019 (COVID­19), has infected more than 410,000 patients globally according to the situation report of World Health Organization. Lung ultrasound is an important tool for the diagnosis and follow-up of pneumonia in neonates, children, and adults [2,3,4]. Recent CT reports demonstrated that most of the lesions were distributed peripherally in the lung, which facilitates detection by lung ultrasound [5, 6]. In this study, we characterize the lung ultrasound findings COVID-19 pneumonia, and study the relationship between the ultrasound findings and clinical severity and the time-course of disease progress. Bedside lung ultrasound was performed to detect B-lines, lung consolidation, and pleural line abnormalities at 5 areas in each lung. Vascular ultrasound was also performed to detect potential deep vein thrombosis

Ultra-processed food consumption and risk of cardiovascular events: a systematic review and dose-response meta-analysisResearch in context

Summary: Background: Ultra-processed food (UPF) consumption continues to increase worldwide. However, evidences from meta-analyses are limited regarding the effects on cardiovascular events (CVEs). Methods: A meta-analysis was performed to assess the dose–response relationship of UPF consumption and CVEs risk (including the morbidity and mortality of cardiovascular causes, and myocardial infarction, stroke, transient ischemic attack, coronary intervention). Databases (PubMed, EMBASE, Cochrane Library, and Web of Science) were searched for observational studies published in English language up to October 24, 2023. Generalized least squares regression and restricted cubic splines were used to estimate the linear/nonlinear relationship. PROSPERO CRD 42023391122. Findings: Twenty studies with 1,101,073 participants and 58,201 CVEs cases with a median follow-up of 12.2 years were included. A positive linear relationship between UPF intake and CVEs risk was identified. In addition, positive correlation between coronary heart disease and UPF consumption in terms of daily serving and daily energy proportion. No significant association of UPF consumption with the risk of cerebrovascular disease was observed. Briefly, 10% increase of UPF by daily weight proportion was associated with a 1.9% increase of CVEs risk (RR = 1.019; 95% CI, 1.007–1.031; P = 0.002), an additional daily serving corresponding to 2.2% CVEs risk increase (RR = 1.022; 95% CI, 1.013–1.031; P < 0.001), and 10% increase by daily energy proportion corresponding to 1.6% CVEs risk increase (RR = 1.016; 95% CI, 1.002–1.030; P = 0.022). Interpretation: UPF consumption were associated with a higher risk of CVEs in the positive linear relationship. Our findings highlight the importance of minimizing UPF consumption for cardiovascular health and might be help to pursue public health policies in control of UPF consumption. Funding: This work was supported by the Key Research and Development Program of Shaanxi Province (2023-ZDLSF-22), the Innovative Talent Support Program of Shaanxi Province (2022KJXX-106), and the Key Research and Development Program of Shaanxi Province (2023-YBSF-424)

Triptolide Inhibits Preformed Fibril-Induced Microglial Activation by Targeting the MicroRNA155-5p/SHIP1 Pathway

Evidence suggests that various forms of α-synuclein- (αSyn-) mediated microglial activation are associated with the progression of Parkinson’s disease. MicroRNA-155-5p (miR155-5p) is one of the most important microRNAs and enables a robust inflammatory response. Triptolide (T10) is a natural anti-inflammatory component, isolated from a traditional Chinese herb. The objective of the current study was to identify the role and potential regulatory mechanism of T10 in αSyn-induced microglial activation via the miR155-5p mediated SHIP1 signaling pathway. Mouse primary microglia were exposed to monomers, oligomers, and preformed fibrils (PFFs) of human wild-type αSyn, respectively. The expressions of TNFα and IL-1β, measured by enzyme-linked immunosorbent assay (ELISA) and qPCR, demonstrated that PFFs initiated the strongest immunogenicity in microglia. Application of inhibitors of toll-like receptor (TLR) 1/2, TLR4, and TLR9 indicated that PFFs activated microglia mainly via the NF-κB pathway by binding TLR1/2 and TLR4. Treatment with T10 significantly suppressed PFF-induced microglial activation and attenuated the release of proinflammatory cytokines including TNFα and IL-1β. Levels of IRAK1, TRAF6, IKKα/β, p-IKKα/β, NF-κB, p-NF-κB, PI3K, p-PI3K, t-Akt, p-Akt and SHIP1 were measured via Western blot. Levels of miR155-5p were measured by qPCR. The results demonstrated that SHIP1 acted as a downstream target molecule of miR155-5p. Treatment with T10 did not alter the expression of IRAK1 and TRAF6, but significantly decreased the expression of miR155-5p, resulting in upregulation of SHIP1 and repression of NF-κB activity, suggesting inhibition of inflammation and microglial activation. The protective effects of T10 were abolished by the use of SHIP1 siRNA and its inhibitor, 3AC, and miR155-5p mimics. In conclusion, our results demonstrated that treatment with T10 suppressed microglial activation and attenuated the release of proinflammatory cytokines by suppressing NF-κB activity via targeting the miR155-5p/SHIP1 pathway in PFFs-induced microglial activation

Engineered fluorescent carbon dots as promising immune adjuvants to efficiently enhance cancer immunotherapy

Engineered fluorescent carbon dots as promising immune adjuvants to efficiently enhance cancer immunotherap