Dexmedetomidine sedation could reduce postoperative delirium and was associated with shorter length of intubation, but might increase bradycardia in patients after cardiac surgery compared with propofol.

Hepatic hepcidin plays an important role in sepsis through regulation of iron metabolism. The findings may have potential therapeutic implications for liver diseases in which hepcidin expression is decreased.

GPR17 is a G (i)-coupled dual receptor, linked to P2Y and CysLT receptors stimulated by uracil nucleotides and cysteinyl leukotrienes, respectively. Recent evidence has demonstrated that GPR17 inhibition ameliorates the progression of cerebral ischemic injury by regulating neuronal death and microglial activation. The present study aimed to assess the detailed regulatory roles of this receptor in oxygen-glucose deprivation/recovery (OGD/R)-induced ischemia-like injury in vitro and explore the underlying mechanism. The results demonstrated that OGD/R induced ischemic neuronal injury and microglial activation, including enhanced phagocytosis and increased inflammatory cytokine release in neuron‑glial mixed cultures of cortical cells. GPR17 upregulation during OGD/R was spatially and temporally correlated with neuronal injury and microglial activation. In addition, GPR17 knockdown inhibited OGD/R-induced responses in neuron-glial mixed cultures. GPR17 knockdown also attenuated cell injury induced by the agonist leukotriene D4 (LTD4) or uridine 5′-diphosphate (UDP) in neuron-glial mixed cultures. However, GPR17 knockdown did not affect OGD/R-induced ischemic neuronal injury in primary cultures of neurons. In primary astrocyte cultures, neither GPR17 nor OGD/R induced injury. By contrast, GPR17 knockdown ameliorated OGD/R-induced microglial activation, boosting phagocytosis and inflammatory cytokine release in primary microglia cultures. Finally, the results demonstrated that the conditioned medium of microglia pretreated with OGD/R induced neuronal death, and the neuronal injury was significantly inhibited by GPR17 knockdown. These findings suggested that GPR17 may mediate ischemia-like neuronal injury and microglial activation in vitro; however, the protective effects on ischemic neuronal injury might depend upon microglial activation. Whether GPR17 regulates neuronal injury mediated by oligodendrocyte linkage remains to be investigated.

Despite being less invasive, patients who underwent video-assisted thoracic surgery (VATS) suffered considerable postoperative pain. Paravertebral block (PVB) was proven to provide effective analgesia in patients with VATS; however, there is no difference in pain relief between preoperative PVB and postoperative PVB. This study was aimed to investigate the analgesic efficacy of combination of preoperative and postoperative PVB on the same patient undergoing VATS. In this prospective, double-blinded, randomized controlled trial, 44 patients undergoing VATS were enrolled, and they received patient-controlled intravenous analgesia (PCIA) with sufentanil plus preoperative PVB (Group A, n = 15) or postoperative PVB (Group B, n = 15), or combination of preoperative and postoperative PVB (Group C, n = 14). The primary outcome was sufentanil consumption and PCIA press times in the first 24 hours postoperatively. Also, data of postoperative use of PCIA and visual analogue scale (VAS) were collected. In the first 24 hours postoperatively, median sufentanil consumption in Group C was 0 (0–34.75) μg, which was much less than that in Group A (45.00 (33.00–47.00) μg, p=0.005) and Group B (36 (20.00–50.00) μg, p=0.023). Patients in Group C pressed less times of PCIA (0 (0–0) times) than patients in Group A (2 (1–6) times, p < 0.001) and Group B (2 (1–3) times, p=0.009). Kaplan–Meier analysis showed patients with combination of preoperative and postoperative PVB had a higher PCIA-free rate than patients with either technique alone (p=0.003). The VAS among the three groups was comparable postoperatively. The combination of both preoperative and postoperative PVB provides better analgesic efficacy during the early postoperative period and may be an alternative option for pain control after VATS. This trial is registered with ChiCTR1800017102.

Background: Hepcidin is a liver-derived master regulator of iron metabolism through its molecular target ferroportin, the only known mammalian iron exporter. Accumulated evidence has shown the important roles of hepatic hepcidin in host defense and infections. Hepcidin is also expressed by airway epithelial cells. However, the function of epithelial hepcidin during bacterial pneumonia remains unknown. Methods: Pneumonia was induced in hepcidin-1-deficient and wild-type mice using the most common bacterial agents, and the effects of hepcidin on survival, bacterial burden, iron status, and macrophage phagocytosis after bacterial pneumonia were assessed. Results: Hepcidin levels decreased in airway epithelium during common pneumonia, while lung macrophage-derived ferroportin levels and pulmonary iron concentrations increased. Lack of hepcidin in the airway epithelium worsened the outcomes of pneumonia. Manipulation of hepcidin level in the airway epithelium in mice with macrophage-specific ferroportin deletion did not affect the progress of pneumonia. Increased pulmonary iron concentration not only facilitated bacterial growth but also led to the defective phagocytic function of lung macrophages via activation of RhoA GTPase through oxidation of RhoGDI. Furthermore, enhancing the hepcidin level in the airway epithelium rescued mice from lethal bacterial pneumonia. Conclusions: These findings identify an uncharacterized important role of airway epithelial hepcidin in protection against bacterial pneumonia and provide the basis for novel alternative therapeutic strategies for combatting bacterial pneumonia in future translational research.