Messenger RNA (mRNA) therapeutics have garnered considerable attention due to their remarkable efficacy in the treatment of various diseases. The COVID‐19 mRNA vaccine and RSV mRNA vaccine have been approved on the market. Due to the inherent nuclease‐instability and negative charge of mRNA, delivery systems are developed to protect the mRNA from degradation and facilitate its crossing cell membrane to express functional proteins or peptides in the cytoplasm. However, the deficiency in transfection efficiency and targeted biological distribution are still the major challenges for the mRNA delivery systems. In this review, we first described the physiological barriers in the process of mRNA delivery and then discussed the design approach and recent advances in mRNA delivery systems with an emphasis on their tissue/cell‐targeted abilities. Finally, we pointed out the existing challenges and future directions with deep insights into the design of efficient mRNA delivery systems. We believe that a high‐precision targeted delivery system can greatly improve the therapeutic effects and bio‐safety of mRNA therapeutics and accelerate their clinical transformations. This review may provide a new direction for the design of mRNA delivery systems and serve as a useful guide for researchers who are looking for a suitable mRNA delivery system.

Although the combination of polymyxin and tigecycline is widely used in treating carbapenem-resistant bacterial infections, the benefit of this combination is still uncertain. To assess whether adding polymyxin B to the high-dose tigecycline regimen would result in better clinical outcomes than the high-dose tigecycline therapy in patients with pneumonia caused by carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii, we conducted a propensity score-matched cohort study in a single center between July 2019 and December 2021. Of the 162 eligible patients, 102 were included in the 1:1 matched cohort. The overall 14-day mortality in the matched cohort was 24.5%. Compared with high-dose tigecycline, the combination therapy was not associated with better clinical outcomes, and showed similar 14-day mortality (OR, 0.72, 95% CI 0.27–1.83, p = 0.486), clinical cure (OR, 1.09, 95% CI 0.48–2.54, p = 0.823), microbiological cure (OR, 0.96, 95% CI 0.39–2.53, p = 0.928) and rate of nephrotoxicity (OR 0.85, 95% CI 0.36–1.99, p = 0.712). Subgroup analyses also did not demonstrate any statistical differences. Based on these results, it is reasonable to recommend against adding polymyxin B to the high-dose tigecycline regimen in treating pneumonia caused by carbapenem-resistant K. pneumoniae and A. baumannii.

Background: The prediction accuracy of pulse pressure variation (PPV) for fluid responsiveness was proposed to be unreliable in low tidal volume (Vt) ventilation. It was suggested that changes in PPV obtained by transiently increasing Vt to 8 ml/kg accurately predicted fluid responsiveness even in subjects receiving low Vt. We assessed whether the changes in PPV induced by a Vt challenge predicted fluid responsiveness in our critically ill subjects ventilated with low Vt 6 ml/kg. Methods: This study is a prospective single-center study. PPV and other parameters were measured at a Vt of 6 mL/kg, 8 mL/kg, and after volume expansion. The prediction accuracy of PPV and other parameters for fluid responsiveness before and after tidal volume challenge was also analyzed using receiver operating characteristic (ROC) curves. Results: Thirty-one of the 76 subjects enrolled in the study were responders (41%). Respiratory system compliance of all subjects decreased significantly (26 ± 4.3). The PPV values were significantly higher in the responder group than the non-responder group before (8.8 ± 2.7 vs 6.8 ± 3.1) or after (13.0 ± 1.7 vs 8.5 ± 3.0) Vt challenge. In the receiver operating characteristic curve (ROC) analysis, PPV₆ showed unsatisfactory predictive capability with an area under the curve (AUC) of 0.69 (95%CI, 0.57–0.79, p = 0.002) at a Vt of 6 mL/kg. PPV₈ andΔPPV_6–8 showed good predictive capability with an AUC of 0.90 (95% CI, 0.81–0.96, p < 0.001) and 0.90 (95% CI, 0.80–0.95, P < 0.001) respectively. The corresponding cutoff values were 11% for PPV₈ and 2% for ΔPPV_6–8. Conclusions: PPV shows a poor operative performance as a predictor of fluid responsiveness in critically ill subjects ventilated with a tidal volume of 6 mL/ kg. Vt challenge could improve the predictive accuracy of PPV to a good but not excellent extent when respiratory system compliance decreased significantly.

Inflammation, a complex biological response against injury or infection, is an important pathological basis for various critical diseases. A “normal” immune response exemplifies a balanced dialogue between immunological cells and a medley of pro- and anti-inflammatory mediators. However, under pathological conditions, this equilibrium is disrupted by the overwhelming release of cytokines, also known as a cytokine storm, which significantly contributes to multiple organ dysfunction and death. Accumulating clinical evidence highlights the efficacy of CytoSorb® hemoadsorption in eliminating damage-associated molecular patterns, pathogen-associated molecular patterns and excessive cytokines from the blood, which underscores the broad use of CytoSorb® in managing various critical conditions. In this narrative review, we conduct a state-of-the-art review of CytoSorb® hemoadsorption in daily critical care practice. By searching ‘CytoSorb®’, ‘cytokine absorption’, ‘hemoadsorption’ and ‘hemoperfusion’ in PubMed, Embase and Web of Science, we discussed the rationale and research progress for cytokine adsorption with CytoSorb® from January 2019 to May 2025. Then, we summarize the latest clinical evidence regarding the use of CytoSorb® in sepsis, cardiac surgery, extracorporeal membrane oxygenation, hepatic diseases, rhabdomyolysis and burn injuries. Finally, we elaborated on the impact of CytoSorb® on the clearance rates of antibiotics and anticoagulants to address its safety concerns and highlighted ongoing debates on the timing, dose and patient selection criteria of CytoSorb® hemoadsorption, which requires future research to optimize actual benefits.