Background: Mesenchymal stem cells (MSCs) have been shown to alleviate acute lung injury (ALI) via paracrine hepatocyte growth factor (HGF) and to induce the differentiation of dendritic cells (DCs) into tolerogenic dendritic cells (DCregs) and participate in the immune response. However, whether MSCs induce the production of DCregs by secreting HGF to alleviate early ALI remains unclear. We observed that the protective effect of mouse bone marrow-derived MSCs against lipopolysaccharide (LPS)-induced ALI was achieved by inducing mature DCs (mDCs) to differentiate into DCregs, and its mechanism is related to the activation of the HGF/Akt pathway. Methods: MSCs or MSCs with overexpression or knockdown of HGF were cocultured with DCs derived from mouse bone marrow using a Transwell system for 3 days. Moreover, we used MSCs or MSCs with overexpression or knockdown of HGF to treat LPS-induced ALI mice for 24 h. Flow cytometry was performed to measure the phagocytosis, accumulation, and maturation of DCs, as well as proliferation of T cells. Lung injury was estimated by lung wet weight to body weight ratio (LWW/BW) and histopathological analysis. Furthermore, we used the Akt inhibitor MK-2206 in a coculture system to elucidate the role of the HGF/Akt pathway in regulating the differentiation of DCs into regulatory DCs and relieving lung injury in early ALI mice. Results: Immature DCs (imDCs) were induced to mature after 24 h of LPS (50 ng/ml) stimulation. MSCs or HGF induced the differentiation of mDCs into regulatory DCs characterized by low expression of MHCII, CD86, and CD40 molecules, strong phagocytic function, and the ability to inhibit T cell proliferation. The effect of MSCs on DCregs was enhanced with the increase in HGF secretion and was weakened with the decrease in HGF secretion. DCregs induced by recombinant HGF were attenuated by the Akt inhibitor MK-2206. Lung DC aggregation and mDC ratio increased in LPS-induced ALI mice, while treatment with MSCs decreased lung DC aggregation and maturation and alleviated lung pathological injury. High expression of the HGF gene enhanced the above effect of MSCs, while decreased expression of HGF weakened the above effect of MSCs. Conclusions: MSCs alleviate early ALI via paracrine HGF by inducing mDCs to differentiate into regulatory DCs. Furthermore, the mechanism of HGF-induced differentiation of mDCs into DCregs is related to the activation of the Akt pathway.

Background: This Bayesian network analysis was performed to assess the effects of different intravenous sedatives on outcomes in adult critically ill patients. Methods: We searched for and gathered data from MEDLINE, Cochrane Central Register of Controlled Trials, Elsevier and Web of Science databases. Bayesian network analysis was performed to evaluate the effect of different intravenous sedatives on outcome in adult critically ill patients. Random errors were evaluated by trial sequential analysis (TSA). Results: Twenty-seven studies including 8,599 critically ill adult patients were enrolled in the analysis. Comparisons among lorazepam, midazolam, propofol, dexmedetomidine, haloperidol and placebo or usual care were presented in a network plot. No significant differences were found for longest mortality in critically ill patients. However, when compared with midazolam, dexmedetomidine had a shorter ICU length of stay and a lower incidence of delirium. Meanwhile, midazolam had a longer ICU length of stay when compared with placebo, propofol and usual care. Subgroup analyses were performed respectively in sepsis, invasive ventilated patients and postoperative patients, as well as patients with higher severity of disease. Lower mortality was found in dexmedetomidine group when compared with placebo in postoperative patients. No differences were found for mortality, ICU length of stay and incidence of delirium in other subgroups. When compared with other sedatives, dexmedetomidine shortened ICU length of stay significantly in ventilated patients. TSA indicated lack of firm evidence for a beneficial effect. Conclusions: No differences were found for longest mortality of different sedatives in adult critically ill patients. However, when compared with midazolam, dexmedetomidine had a shorter ICU length of stay and a lower incidence of delirium. TSA indicated lack of firm evidence for the results. More powered, randomized, controlled trials are needed to determine the effects.

Background: Effective antibiotic management is crucial for ICU patients with pulmonary infections. However, guidelines are unclear whether the optimal strategy is multiple cultures on the infection onset day or a single daily culture to guide antibiotic therapy. Methods: This study involved 362 ICU patients with confirmed pulmonary infections, categorized into a "multiple-daily" group (≥2 cultures within 24 hours) and a "once-daily" group (1 culture per 24 hours). Propensity score matching was used to balance baseline characteristics. Primary outcome was antibiotic adjustment rate. Secondary outcomes included mechanical ventilation duration, ICU and total hospital length of stay, hospitalization costs, and mortality. Results: The multiple-daily group had more frequent antibiotic adjustments both before and after matching (76.88% vs 67.33%, p = 0.048 pre-matching; p = 0.076 post-matching). The once-daily group experienced significantly shorter durations of mechanical ventilation (pre: 119.50 vs 159.50 hours; post: 116.00 vs 156.00 hours; both p < 0.001), ICU stay (pre: 10.00 vs 13.00 days; post: 9.00 vs 13.00 days; both p < 0.001), and lower hospitalization costs (pre: 138,150 vs 167,910 CNY, p = 0.011; post: 136,870 vs 167,780 CNY, p = 0.004). The hospital stay was also shorter in the once-daily group, with similar mortality rates between groups. Common multidrug-resistant pathogens included CRAB (32.52%), MRSA (24.39%), ESBL (18.70%), CRPA (15.45%), and CRE (12.00%). The multiple-daily group had higher detection rates of CRAB (38.46% vs 25.86%, p=0.050) and MRSA (30.77% vs 17.24%, p=0.048), with more frequent antibiotic adjustments, especially in multidrug-resistant cases (87.69% vs 70.69%, p=0.019). Conclusion: In ICU patients with pulmonary infections, multiple-daily sputum cultures lead to more frequent antibiotic adjustments and better detection of multidrug-resistant pathogens. However, a once-daily culture strategy is associated with reduced healthcare resource utilization and comparable mortality. Further randomized trials are needed to determine the optimal sputum culture frequency in the ICU setting. Trial Registration: This study was registered with the Chinese Clinical Trial Registry under the registration number ChiCTR2400091085.

Objective: To develop and validate a nomogram-based predictive model for in-hospital mortality among patients with liver cirrhosis complicated by sepsis, and to evaluate its predictive accuracy.Methods: Clinical data were retrospectively collected from patients diagnosed with liver cirrhosis and sepsis who were admitted to the Fuyang Infectious Disease Clinical College of Anhui Medical University between January 2018 and July 2025. Patients were classified into the Survivor group or the Non-survivor group. The dataset was randomly divided into a training set (70%) and a validation set (30%). Potential predictors were identified through univariate and multivariate logistic regression analyses, and a predictive model was subsequently developed using Lasso regression. The model was visualized as a nomogram, and its performance was rigorously evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA) to assess its clinical utility.Results: A total of 264 patients were enrolled in this study. Among the 188 patients in the training set, 54 (28.7%) died during hospitalization, while 21 out of 76 patients (27.6%) in the validation set experienced in-hospital mortality. Multivariate logistic regression analysis identified alcoholic cirrhosis, Child-Pugh score, mechanical ventilation, TBiL and HR as independent predictors of in-hospital mortality (all P < 0.05). The nomogram model demonstrated robust predictive performance, with ROC analysis showing an area under the curve (AUC) of 0.81 (95% CI: 0.75–0.81) in the training set and 0.83 (95% CI: 0.73–0.92) in the validation set. Calibration plots revealed that the model's predictions closely aligned with the ideal reference line. DCA showed that the model provided significant clinical net benefit across a wide range of threshold probabilities.Conclusion: The nomogram model developed using Lasso regression appears to demonstrate promising predictive potential for in-hospital mortality in patients with liver cirrhosis complicated by sepsis. This tool may offer valuable support for clinical decision-making and could potentially aid in guiding early interventions for patients identified as higher risk.