Introduction: Early diagnosis of sepsis is vital to the clinical course and outcome of septic patients. Recently, soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) appears to be a potential marker of infection. The objective of this systematic review and meta-analysis was to evaluate the accuracy of plasma sTREM-1 for sepsis diagnosis in systemic inflammatory patients. Methods: A systematic literature search of PubMed, Embase and Cochrane Central Register of Controlled Trials was performed using specific search terms (up to 15 October 2012). Studies were included if they assessed the accuracy of plasma sTREM-1 for sepsis diagnosis in adult patients with systemic inflammatory response syndrome (SIRS) and provided sufficient information to construct a 2 X 2 contingency table. Results: Eleven studies with a total of 1,795 patients were included. The pooled sensitivity and specificity was 79% (95% confidence interval (CI), 65 to 89) and 80% (95% CI, 69 to 88), respectively. The positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 4.0 (95% CI, 2.4 to 6.9), 0.26 (95% CI, 0.14 to 0.48), and 16 (95% CI, 5 to 46), respectively. The area under the curve of the summary receiver operator characteristic was 0.87 (95% CI, 0.84 to 0.89). Meta-regression analysis suggested that patient sample size and assay method were the main sources of heterogeneity. Publication bias was suggested by an asymmetrical funnel plot (P = 0.02). Conclusions: The present meta-analysis showed that plasma sTREM-1 had a moderate diagnostic performance in differentiating sepsis from SIRS. Accordingly, plasma sTREM-1 as a single marker was not sufficient for sepsis diagnosis in systemic inflammatory patients.

While host miRNA usually plays an antiviral role, the relentless tides of viral evolution have carved out a mechanism to recruit host miRNA as a viral protector. By complementing miR-122 at the 5′ end of the genome, the hepatitis C virus (HCV) gene can form a complex with Argonaute 2 (Ago2) protein to protect the 5′ end of HCV RNA from exonucleolytic attacks. Experiments showed that the disruption of the stem-loop 1(SL1) structure and the 9th nucleotide (T9) of HCV site 1 RNA could enhance the affinity of the Ago2 protein to the HCV site 1 RNA (target RNA). However, the underlying mechanism of how the conformation and dynamics of the Ago2: miRNA: target RNA complex is affected by the SL1 and T9 remains unclear. To address this, we performed large-scale molecular dynamics simulations on the AGO2-miRNA complex binding with the WT target, T9-abasic target and SL1-disruption target, respectively. The results revealed that the T9 and SL1 structures could induce the departing motion of the PAZ, PIWI and N domains, propping up the mouth of the central groove which accommodates the target RNA, causing the instability of the target RNA and disrupting the Ago2 binding. The coordinated motion among the PAZ, PIWI and N domains were also weakened by the T9 and SL1 structures. Moreover, we proposed a new model wherein the Ago2 protein could adopt a more constraint conformation with the proximity and more correlated motions of the PAZ, N and PIWI domains to protect the target RNA from dissociation. These findings reveal the mechanism of the Ago2-miRNA complex’s protective effect on the HCV genome at the atomic level, which will offer guidance for the design of drugs to confront the protection effect and engineering of Ago2 as a gene-regulation tool.

Postoperative cognitive dysfunction (POCD) in older adults is strongly linked to neuroinflammation driven by microglial activation and NF-κB signaling. Runx1 has emerged as an upstream regulator of NF-κB, but its role in POCD is unknown. Dendrobine, a sesquiterpenoid alkaloid from Dendrobium species, exhibits anti-inflammatory and neuroprotective activity. POCD was induced in aged C57BL/6 mice via sevoflurane anesthesia combined with exploratory laparotomy. Dendrobine (10 or 20 mg/kg) was administered, and cognitive outcomes were evaluated by Morris Water Maze and Novel Object Recognition. RNA sequencing, Western blotting, immunofluorescence, and in vitro microglia-neuron co-culture systems were employed to investigate inflammatory responses, apoptosis, synaptic plasticity, and signaling pathway activation. Functional roles of Runx1 were validated via siRNA knockdown, pharmacological inhibition (Ro5-3335), and overexpression in BV2 cells. Dendrobine improved spatial and recognition memory in POCD mice, reduced hippocampal microglial activation, proinflammatory cytokine expression (TNF-α, IL-1β, IL-6), and neuronal apoptosis while enhancing synaptic protein levels (BDNF, PSD95, SYN1). Transcriptomic and KEGG analyses revealed suppression of NF-κB signaling by dendrobine, with Runx1 identified as an upstream modulator. Dendrobine downregulated Runx1 expression in vivo and in vitro. Runx1 inhibition enhanced dendrobine's anti-inflammatory effects, whereas RUNX1 overexpression abolished them. Dendrobine ameliorates POCD by inhibiting the Runx1/NF-κB signaling pathway, suppressing neuroinflammation, promoting synaptic resilience, and preventing neuronal apoptosis. Runx1 appears to act as a key upstream mediator of NF-κB signaling in POCD. Targeting the Runx1/NF-κB axis represents a promising strategy for perioperative neuroprotection.

Hypoxemia is a common adverse event during propofol sedation for gastrointestinal endoscopy. Maintaining a sufficiently slow infusion rate is known to reduce respiratory depression caused by propofol, but achieving this consistently is challenging due to variations in manual techniques. This study evaluated the use of a narrow-bore extension tube to administer propofol, which passively slows infusion, to reduce hypoxemia during gastroscopy sedation. A randomized controlled trial was conducted among patients undergoing propofol sedation for gastroscopy. Participants were assigned to either the narrow-bore extension tube group, which restricts infusion rates, or the control group receiving a standard-bore extension tube with unrestricted infusion rates. The primary outcome was the incidence of hypoxemia (SpO2 < 90%), with secondary outcomes including severe hypoxemia (SpO2 < 90% for ≥ 60 s or SpO2 < 75%), time to achieve deep sedation, total propofol dosage, and the incidence of pain on propofol injection (POPI). Subgroup analyses by age and BMI were performed. The incidence of hypoxemia was significantly lower in the narrow-bore extension tube (11.7% vs. 27.0%, p = 0.001), and there was a corresponding decrease in severe hypoxemia (7.3% vs. 19.7%, p = 0.003). The median time to achieve deep sedation was longer in the narrow-bore group (70 vs. 54 s; p < 0.001). The greatest reduction in hypoxemia was observed in overweight patients (BMI 25–28 kg/m2, p = 0.029). Using a narrow-bore extension tube to control propofol infusion rates significantly reduces hypoxemia during gastroscopy sedation. This cost-effective strategy is especially beneficial for higher-risk patients, such as those who are overweight. The clinical trial was registered on Chinese Clinical Trial Register on December 16, 2024 (ChiCTR2400094042).